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1.
Adv Gerontol ; 32(3): 357-363, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31512421

RESUMO

The aim of this work was to examine the content of Piezo1 in fibroblasts and blood vessels of human dermis from the development until deep aging (from 20 weeks of pregnancy until 85 years old), and defining of a role of Piezo1 in age-dependent changes in the number of fibroblasts and blood vessels in the dermis. Piezo1, proliferating cells nuclear antigen (PCNA), endothelial cells marker CD31 were detected with indirect immunohistochemical technique. Results showed that a portion of fibroblasts with positive staining for Piezo1 in the dermis is decreased from 20 weeks of pregnancy to 40 years old. Percent of Piezo1 positive fibroblasts in dermis is increased sufficiently since 41 years old until 60-85 years old group. The content of Piezo1 in blood vessels in the human dermis is decreased sufficiently from 20 weeks of pregnancy until 40 years old. Age-related changes in the content of Piezo1 in fibroblasts and blood vessels is not associated with an age-related decrease in total number and percent of PCNA positive fibroblasts, the number of blood vessels in the dermis.


Assuntos
Vasos Sanguíneos , Derme , Fibroblastos , Canais Iônicos , Envelhecimento da Pele , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasos Sanguíneos/fisiologia , Criança , Pré-Escolar , Derme/irrigação sanguínea , Derme/citologia , Derme/embriologia , Derme/crescimento & desenvolvimento , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Lactente , Canais Iônicos/metabolismo , Masculino , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Gravidez , Antígeno Nuclear de Célula em Proliferação/metabolismo , Envelhecimento da Pele/fisiologia
2.
Int J Mol Sci ; 20(16)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412620

RESUMO

Two mesenchymal zinc transporters, ZIP7 and ZIP13, play critical roles in dermal development. ZIP7 and ZIP13 are the closest among the conserved mammalian zinc transporters. However, whether their functions are complementary remains a controversial issue. In the present study, we found that the expression of ZIP13, but not ZIP7, is elevated by transforming growth factor beta (TGF-ß) treatment, indicating that TGF-ß-mediated ZIP13 amplification is crucial for collagen production during dermal development. Genome-wide gene expression analysis revealed that ~26% of genes are dependent on either ZIP7 or ZIP13, which is greater than the ~17% of genes dependent on both of them. ZIP7 depletion induces endoplasmic reticulum (ER) stress in mesenchymal stem cells, resulting in significant inhibition of fibrogenic differentiation. However, ZIP13 depletion does not induce ER stress. Though both ZIP7 and ZIP13 contain traditional ER signal peptides for their intracellular localization, their distributions are distinct. When ZIP7 and ZIP13 are coexpressed, their localizations are distinct; ZIP7 is located on the ER, but ZIP13 is located on both the ER and Golgi, indicating that only ZIP13 is a zinc gatekeeper on the Golgi. Our data illustrate that the different actions of ZIP7 and ZIP13 are crucial for dermal development.


Assuntos
Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Derme/embriologia , Derme/metabolismo , Organogênese/genética , Zinco/metabolismo , Animais , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Genoma , Estudo de Associação Genômica Ampla , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Knockout , Modelos Biológicos
3.
EMBO J ; 37(22)2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30297530

RESUMO

Endothelial cells line blood and lymphatic vessels and form intercellular junctions, which preserve vessel structure and integrity. The vascular endothelial cadherin, VE-cadherin, mediates endothelial adhesion and is indispensible for blood vessel development and permeability regulation. However, its requirement for lymphatic vessels has not been addressed. During development, VE-cadherin deletion in lymphatic endothelial cells resulted in abortive lymphangiogenesis, edema, and prenatal death. Unexpectedly, inducible postnatal or adult deletion elicited vessel bed-specific responses. Mature dermal lymph vessels resisted VE-cadherin loss and maintained button junctions, which was associated with an upregulation of junctional molecules. Very different, mesenteric lymphatic collectors deteriorated and formed a strongly hyperplastic layer of lymphatic endothelial cells on the mesothelium. This massive hyperproliferation may have been favored by high mesenteric VEGF-C expression and was associated with VEGFR-3 phosphorylation and upregulation of the transcriptional activator TAZ Finally, intestinal lacteals fragmented into cysts or became highly distended possibly as a consequence of the mesenteric defects. Taken together, we demonstrate here the importance of VE-cadherin for lymphatic vessel development and maintenance, which is however remarkably vessel bed-specific.


Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Derme/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Linfangiogênese , Vasos Linfáticos/metabolismo , Mesentério/embriologia , Animais , Antígenos CD/genética , Caderinas/genética , Células Endoteliais/metabolismo , Deleção de Genes , Camundongos , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
4.
Methods Mol Biol ; 1846: 19-35, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30242750

RESUMO

The capacity to visualize the lymphatic vasculature in three-dimensions has revolutionized our understanding of the morphogenetic mechanisms important for constructing the lymphatic vascular network during development. Two complementary approaches are commonly employed to assess the function of genes and signaling pathways important for development of the dermal lymphatic vasculature in the mouse embryo. The first of these is whole-mount immunostaining of embryonic skin to analyze dermal lymphatic vessel network patterning and morphology in two and three dimensions. The second is immunostaining of thin tissue sections to examine lymphatic vessel identity, lumen formation and protein localization within discrete lymphatic endothelial cells in a two-dimensional setting. Here we present detailed protocols for multicolor immunofluorescent immunostaining of embryonic dorsal skin and thin tissue cryosections. Each of these methods generates high-resolution images of the dermal lymphatic vasculature, yielding information integral to in-depth characterization of lymphatic vessel phenotypes in the developing mouse embryo.


Assuntos
Angiografia , Derme/irrigação sanguínea , Linfangiogênese , Vasos Linfáticos/diagnóstico por imagem , Animais , Derme/embriologia , Feminino , Imunofluorescência , Camundongos , Microscopia Confocal
5.
Poult Sci ; 97(9): 3236-3247, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29790972

RESUMO

The skin is a natural target of stem cell research because of its large size and easy accessibility. Cutaneous mesenchymal stem cells have shown to be a promising source of various adult stem cell or progenitor cell populations, which provide an important source of stem cell-based investigation. Nowadays, much work has been done on dermal-derived mesenchymal stem cells (DMSCs) from humans, mice, sheep, and other mammals, but the literature on avian species has been rarely reported. As an animal model, the goose is an endemic species abounding in dermal tissues which is important in the global economy. In this study, we isolated and established the mesenchymal stem cell line from dermis tissue of goose, which were subcultured to passage 21 in vitro without loss of their functional integrity in terms of morphology, renewal capacity, and presence of mesenchymal stem cell markers. Cryopreservation and resuscitation were also observed in different passages. To investigate the biological characteristics of goose DMSCs, immunofluorescence, reverse transcription-polymerase chain reaction, and flow cytometry were used to detect the characteristic surface markers. Growth curves and the capacity of colony forming were performed to test the self-renew and proliferative ability. Furthermore, the DMSCs are induced to osteoblasts, adipocytes, and chondrocytes in vitro. Our results suggest that DMSCs isolated from goose embryos possess similar biological characteristics to those from other species. The methods in establishment and cultivation of goose DMSCs line demonstrated a good self-renew and expansion potential in vitro, which provided a technological platform for preserving the valuable genetic resources of poultry and a great inspiration for in vitro investigation of avian MSCs.


Assuntos
Diferenciação Celular , Derme/embriologia , Embrião não Mamífero/metabolismo , Gansos/fisiologia , Células-Tronco Mesenquimais/metabolismo , Animais , Técnicas de Cultura de Células/veterinária , Células Cultivadas , Projetos Piloto
6.
Artigo em Inglês | MEDLINE | ID: mdl-29244903

RESUMO

The skin is the largest organ of the body and is composed of two layers: the overlying epidermis and the underlying dermis. The dermal fibroblasts originate from distinct locations of the embryo and contain the positional identity and patterning information in the skin. The dermal fibroblast progenitors differentiate into various cell types that are fated to perform specific functions such as hair follicle initiation and scar formation during wound healing. Recent studies have revealed the heterogeneity and plasticity of dermal fibroblasts within skin, which has implications for skin disease and tissue engineering. The objective of this review is to frame our current understanding and provide new insights on the origin and differentiation of dermal fibroblasts and their function during cutaneous development and healing. WIREs Dev Biol 2018, 7:e307. doi: 10.1002/wdev.307 This article is categorized under: Birth Defects > Organ Anomalies Signaling Pathways > Cell Fate Signaling Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Nervous System Development > Vertebrates: Regional Development.


Assuntos
Diferenciação Celular , Cicatriz/metabolismo , Derme/citologia , Fibroblastos/citologia , Animais , Derme/embriologia , Derme/metabolismo , Derme/patologia , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Fibroblastos/metabolismo , Humanos
7.
Stem Cell Reports ; 9(5): 1477-1487, 2017 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-29033303

RESUMO

The embryonic origin of lineage precursors of the trunk dermis is somewhat controversial. Precursor cells traced by Myf5 and Twist2 (Dermo1) promoter activation (i.e., cells of presumed dermomyotomal lineage) have been reported to generate Schwann cells. On the other hand, abundant data demonstrate that dermal Schwann cells derive from the neural crest. This is relevant because dermal precursors give rise to neural lineages, and multilineage differentiation potential qualifies them as adult stem cells. However, it is currently unclear whether neural lineages arise from dedifferentiated Schwann cells instead of mesodermally derived dermal precursor cells. To clarify these discrepancies, we traced SOX2+ adult dermal precursor cells by two independent Myf5 lineage tracing strains. We demonstrate that dermal Schwann cells do not belong to the Myf5+ cell lineage, indicating that previous tracing data reflected aberrant cre recombinase expression and that bona fide Myf5+ dermal precursors cannot transdifferentiate to neural lineages in physiological conditions.


Assuntos
Linhagem da Célula , Derme/citologia , Células-Tronco Embrionárias Murinas/citologia , Fator Regulador Miogênico 5/metabolismo , Células de Schwann/citologia , Animais , Células Cultivadas , Derme/embriologia , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Fator Regulador Miogênico 5/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Células de Schwann/metabolismo
8.
Development ; 144(10): 1887-1895, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28512199

RESUMO

SOX family proteins SOX2 and SOX18 have been reported as being essential in determining hair follicle type; however, the role they play during development remains unclear. Here, we demonstrate that Sox18 regulates the normal differentiation of the dermal papilla of all hair types. In guard (primary) hair dermal condensate (DC) cells, we identified transient Sox18 in addition to SOX2 expression at E14.5, which allowed fate tracing of primary DC cells until birth. Similarly, expression of Sox18 was detected in the DC cells of secondary hairs at E16.5 and in tertiary hair at E18.5. Dominant-negative Sox18 mutation (opposum) did not prevent DC formation in any hair type. However, it affected dermal papilla differentiation, restricting hair formation especially in secondary and tertiary hairs. This Sox18 mutation also prevented neonatal dermal cells or dermal papilla spheres from inducing hair in regeneration assays. Microarray expression studies identified WNT5A and TNC as potential downstream effectors of SOX18 that are important for epidermal WNT signalling. In conclusion, SOX18 acts as a mesenchymal molecular switch necessary for the formation and function of the dermal papilla in all hair types.


Assuntos
Diferenciação Celular/genética , Folículo Piloso/embriologia , Cabelo/embriologia , Fatores de Transcrição SOXF/fisiologia , Animais , Derme/embriologia , Derme/metabolismo , Embrião de Mamíferos , Células Epidérmicas , Epiderme/embriologia , Feminino , Genes Dominantes , Genes de Troca/fisiologia , Cabelo/metabolismo , Folículo Piloso/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Fatores de Transcrição SOXF/genética
9.
Development ; 143(22): 4193-4202, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27697906

RESUMO

Cellular migrations through constricted spaces are a crucial aspect of many developmental and disease processes including hematopoiesis, inflammation and metastasis. A limiting factor in these events is nuclear deformation. Here, we establish an in vivo model in which nuclei can be visualized while moving through constrictions and use it to elucidate mechanisms for nuclear migration. C. elegans hypodermal P-cell larval nuclei traverse a narrow space that is about 5% their width. This constriction is blocked by fibrous organelles, structures that pass through P cells to connect the muscles to cuticle. Fibrous organelles are removed just prior to nuclear migration, when nuclei and lamins undergo extreme morphological changes to squeeze through the space. Both actin and microtubule networks are organized to mediate nuclear migration. The LINC complex, consisting of the SUN protein UNC-84 and the KASH protein UNC-83, recruits dynein and kinesin-1 to the nuclear surface. Both motors function in P-cell nuclear migration, but dynein, functioning through UNC-83, plays a more central role as nuclei migrate towards minus ends of polarized microtubule networks. Thus, the nucleoskeleton and cytoskeleton are coordinated to move nuclei through constricted spaces.


Assuntos
Citoesqueleto de Actina/metabolismo , Caenorhabditis elegans , Núcleo Celular/metabolismo , Derme/embriologia , Derme/metabolismo , Microtúbulos/metabolismo , Actinas/metabolismo , Animais , Animais Geneticamente Modificados , Transporte Biológico , Padronização Corporal , Caenorhabditis elegans/citologia , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Citoesqueleto/metabolismo , Derme/ultraestrutura , Embrião não Mamífero
10.
Genesis ; 54(8): 415-30, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27265328

RESUMO

Embryonic dermal fibroblasts in the skin have the exceptional ability to initiate hair follicle morphogenesis and contribute to scarless wound healing. Activation of the Wnt signaling pathway is critical for dermal fibroblast fate selection and hair follicle induction. In humans, mutations in Wnt pathway components and target genes lead to congenital focal dermal hypoplasias with diminished hair. The gene expression signature of embryonic dermal fibroblasts during differentiation and its dependence on Wnt signaling is unknown. Here we applied Shannon entropy analysis to identify the gene expression signature of mouse embryonic dermal fibroblasts. We used available human DNase-seq and histone modification ChiP-seq data on various cell-types to demonstrate that genes in the fibroblast cell identity signature can be epigenetically repressed in other cell-types. We found a subset of the signature genes whose expression is dependent on Wnt/ß-catenin activity in vivo. With our approach, we have defined and validated a statistically derived gene expression signature that may mediate dermal fibroblast identity and function in development and disease. genesis 54:415-430, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Diferenciação Celular , Derme/citologia , Fibroblastos/metabolismo , Transcriptoma , Via de Sinalização Wnt/genética , Animais , Derme/embriologia , Fibroblastos/citologia , Regulação da Expressão Gênica no Desenvolvimento , Camundongos
11.
Dev Biol ; 413(1): 60-9, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-26968353

RESUMO

Sensory dendrite morphogenesis is directed by intrinsic and extrinsic factors. The extracellular environment plays instructive roles in patterning dendrite growth and branching. However, the molecular mechanism is not well understood. In Caenorhabditis elegans, the proprioceptive neuron PVD forms highly branched sensory dendrites adjacent to the hypodermis. We report that receptor tyrosine phosphatase CLR-1 functions in the hypodermis to pattern the PVD dendritic branches. Mutations in clr-1 lead to loss of quaternary branches, reduced secondary branches and increased ectopic branches. CLR-1 is necessary for the dendrite extension but not for the initial filopodia formation. Its role is dependent on the intracellular phosphatase domain but not the extracellular adhesion domain, indicating that it functions through dephosphorylating downstream factors but not through direct adhesion with neurons. Genetic analysis reveals that clr-1 also functions in parallel with SAX-7/DMA-1 pathway to control PVD primary dendrite development. We provide evidence of a new environmental factor for PVD dendrite morphogenesis.


Assuntos
Proteínas de Caenorhabditis elegans/fisiologia , Dendritos/metabolismo , Proteínas Tirosina Fosfatases Semelhantes a Receptores/fisiologia , Pele/embriologia , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/metabolismo , Derme/embriologia , Proteínas de Fluorescência Verde/metabolismo , Mutação , Moléculas de Adesão de Célula Nervosa/metabolismo , Neurônios/metabolismo , Fosforilação , Estrutura Terciária de Proteína , Pseudópodes/metabolismo , Células Receptoras Sensoriais/metabolismo , Transgenes
12.
Stem Cells Transl Med ; 4(10): 1187-98, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26253713

RESUMO

UNLABELLED: The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. SIGNIFICANCE: Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides analysis of the current state-of-the-art regenerative approaches using human-derived dermal stem cells, with consideration of current guidelines, to assist translation toward therapeutic use.


Assuntos
Células-Tronco Adultas , Derme/citologia , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Adulto , Células-Tronco Adultas/citologia , Células-Tronco Adultas/imunologia , Células-Tronco Adultas/transplante , Diferenciação Celular , Linhagem da Célula , Separação Celular/métodos , Transplante de Células/efeitos adversos , Derme/embriologia , Camadas Germinativas/citologia , Humanos , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/imunologia , Células-Tronco Multipotentes/transplante , Nicho de Células-Tronco , Transplante Autólogo/métodos
13.
Exp Dermatol ; 24(6): 468-70, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25708924

RESUMO

Embryonic hair follicle (HF) induction and formation is dependent on signalling crosstalk between the dermis and specialized dermal condensates on the mesenchymal side and epidermal cells and incipient placodes on the epithelial side, but the precise nature and succession of signals remain unclear. Platelet-derived growth factor (PDGF) signalling is involved in the development of several organs and the maintenance of adult tissues, including HF regeneration in the hair cycle. As both PDGF receptors, PDGFRα and PDGFRß, are expressed in embryonic dermis and dermal condensates, we explored in this study the role of PDGF signalling in HF induction and formation in the developing skin mesenchyme. We conditionally ablated both PDGF receptors with Tbx18(Cre) in early dermal condensates before follicle formation, and with Prx1-Cre broadly in the ventral dermis prior to HF induction. In both PDGFR double mutants, HF induction and formation ensued normally, and the pattern of HF formation and HF numbers were unaffected. These data demonstrate that mesenchymal PDGF signalling, either in the specialized niche or broadly in the dermis, is dispensable for HF induction and formation.


Assuntos
Derme/embriologia , Folículo Piloso/embriologia , Morfogênese/fisiologia , Fator de Crescimento Derivado de Plaquetas/fisiologia , Transdução de Sinais/fisiologia , Animais , Derme/citologia , Derme/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes , Folículo Piloso/citologia , Folículo Piloso/fisiologia , Mesoderma/citologia , Mesoderma/embriologia , Mesoderma/fisiologia , Camundongos , Camundongos Mutantes , Modelos Animais , Morfogênese/genética , Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/fisiologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/fisiologia , Transdução de Sinais/genética
14.
Exp Gerontol ; 55: 143-51, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24768823

RESUMO

Present research is aimed to examine the number of dermal blood vessels, vascular endothelial growth factor (VEGF), delta-like ligand 4(Dll4) and Jagged-1 (Jag-1) in dermal blood vessels of human from 20weeks of pregnancy to 85years old. Numbers and proliferative activity of dermal fibroblast-like cells were also examined. Blood vessels were viewed with immunohistochemical staining for von Willebrand factor or CD31. VEGF, Dll4, Jag-1, and proliferating cell nuclear antigen (PCNA) were detected immunohistochemically. Results showed that the numbers of fibroblast-like cells, PCNA positive fibroblast-like cells, von Willebrand factor positive or CD31 positive blood vessels in dermis are dramatically decreased with age. The intensity of immunohistochemical staining for VEGF or Jag-1 in blood vessels of dermis is increased from antenatal to deep old period. The degree of immunohistochemical staining of dermal blood vessels for Dll4 has gone up from 20-40weeks of pregnancy to early life period (0-20years), and further decreased below antenatal values. Age-related decrease in the number of dermal blood vessels is suggested to be due to an impairment of VEGF signaling and to be mediated by Dll4 and Jag-1. It may be supposed that diminishing in blood supply of dermis occurring with age is a cause of a decrease in the number and proliferative pool of dermal fibroblasts.


Assuntos
Envelhecimento/fisiologia , Derme/irrigação sanguínea , Neovascularização Fisiológica/fisiologia , Envelhecimento da Pele/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Contagem de Células , Criança , Pré-Escolar , Derme/citologia , Derme/embriologia , Derme/metabolismo , Feminino , Feto/irrigação sanguínea , Feto/metabolismo , Fibroblastos/citologia , Humanos , Lactente , Recém-Nascido , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1 , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Serrate-Jagged , Caracteres Sexuais , Envelhecimento da Pele/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de von Willebrand/metabolismo
15.
PLoS One ; 9(3): e92679, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24671096

RESUMO

The embryonic origin of the dermis in vertebrates can be traced back to the dermomyotome of the somites, the lateral plate mesoderm and the neural crest. The dermal precursors directly overlying the neural tube display a unique dense arrangement and are the first to induce skin appendage formation in vertebrate embryos. These dermal precursor cells have been shown to derive from the dorsomedial lip of the dermomyotome (DML). Based on its expression pattern in the DML, Wnt11 is a candidate regulator of dorsal dermis formation. Using EGFP-based cell labelling and time-lapse imaging, we show that the Wnt11 expressing DML is the source of the dense dorsal dermis. Loss-of-function studies in chicken embryos show that Wnt11 is indeed essential for the formation of dense dermis competent to support cutaneous appendage formation. Our findings show that dermogenic progenitors cannot leave the DML to form dense dorsal dermis following Wnt11 silencing. No alterations were noticeable in the patterning or in the epithelial state of the dermomyotome including the DML. Furthermore, we show that Wnt11 expression is regulated in a manner similar to the previously described early dermal marker cDermo-1. The analysis of Wnt11 mutant mice exhibits an underdeveloped dorsal dermis and strongly supports our gene silencing data in chicken embryos. We conclude that Wnt11 is required for dense dermis and subsequent cutaneous appendage formation, by influencing the cell fate decision of the cells in the DML.


Assuntos
Movimento Celular , Galinhas/metabolismo , Derme/citologia , Derme/embriologia , Células-Tronco/citologia , Proteínas Wnt/metabolismo , Animais , Biomarcadores/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Embrião de Galinha , Regulação da Expressão Gênica no Desenvolvimento , Folículo Piloso/citologia , Camundongos Knockout , Interferência de RNA , Transdução de Sinais , Células-Tronco/metabolismo
16.
Cell Transplant ; 23(10): 1169-85, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23768775

RESUMO

We report that cells from human fetal dermis, termed here multipotent fetal dermal cells, can be isolated with high efficiency by using a nonenzymatic, cell outgrowth method. The resulting cell population was consistent with the definition of mesenchymal stromal cells by the International Society for Cellular Therapy. As multipotent fetal dermal cells proliferate extensively, with no loss of multilineage differentiation potential up to passage 25, they may be an ideal source for cell therapy to repair damaged tissues and organs. Multipotent fetal dermal cells were not recognized as targets by T lymphocytes in vitro, thus supporting their feasibility for allogenic transplantation. Moreover, the expansion protocol did not affect the normal phenotype and karyotype of cells. When compared with adult dermal cells, fetal cells displayed several advantages, including a greater cellular yield after isolation, the ability to proliferate longer, and the retention of differentiation potential. Interestingly, multipotent fetal dermal cells expressed the pluripotency marker SSEA4 (90.56 ± 3.15% fetal vs. 10.5 ± 8.5% adult) and coexpressed mesenchymal and epithelial markers (>80% CD90(+)/CK18(+) cells), coexpression lacking in the adult counterparts isolated under the same conditions. Multipotent fetal dermal cells were able to form capillary structures, as well as differentiate into a simple epithelium in vitro, indicating skin regeneration capabilities.


Assuntos
Derme/citologia , Células-Tronco Fetais/citologia , Células-Tronco Multipotentes/citologia , Diferenciação Celular/fisiologia , Derme/embriologia , Feminino , Humanos , Masculino
17.
Nature ; 504(7479): 277-281, 2013 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-24336287

RESUMO

Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibres of the extracellular matrix (ECM). Even within a single tissue, fibroblasts exhibit considerable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different environmental factors. Here we show, using transplantation assays and lineage tracing in mice, that the fibroblasts of skin connective tissue arise from two distinct lineages. One forms the upper dermis, including the dermal papilla that regulates hair growth and the arrector pili muscle, which controls piloerection. The other forms the lower dermis, including the reticular fibroblasts that synthesize the bulk of the fibrillar ECM, and the preadipocytes and adipocytes of the hypodermis. The upper lineage is required for hair follicle formation. In wounded adult skin, the initial wave of dermal repair is mediated by the lower lineage and upper dermal fibroblasts are recruited only during re-epithelialization. Epidermal ß-catenin activation stimulates the expansion of the upper dermal lineage, rendering wounds permissive for hair follicle formation. Our findings explain why wounding is linked to formation of ECM-rich scar tissue that lacks hair follicles. They also form a platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease.


Assuntos
Linhagem da Célula , Fibroblastos/citologia , Pele/citologia , Pele/crescimento & desenvolvimento , Cicatrização/fisiologia , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Derme/anatomia & histologia , Derme/citologia , Derme/embriologia , Derme/crescimento & desenvolvimento , Feminino , Fibroblastos/transplante , Folículo Piloso/citologia , Folículo Piloso/metabolismo , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Transgênicos , Músculo Liso/citologia , Músculo Liso/metabolismo , Pele/anatomia & histologia , Pele/embriologia , beta Catenina/metabolismo
18.
J Invest Dermatol ; 133(10): 2306-2308, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24030645

RESUMO

Functional testing of dermal papilla (DP) signaling inputs into hair follicle (HF) morphogenesis and regeneration is becoming possible with the advent of new Cre lines. Targeted deletion of the signature genes in early DP precursors has revealed significant signaling redundancy during HF morphogenesis. Furthermore, the DP lineage commitment program can be exploited for generating highly inductive DP cells to be used in HF bioengineering assays.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Derme/embriologia , Folículo Piloso/embriologia , Folículo Piloso/metabolismo , Cabelo/crescimento & desenvolvimento , Lipase/genética , Morfogênese/fisiologia , Diester Fosfórico Hidrolases/genética , Fatores de Transcrição SOXB1/metabolismo , Animais , Feminino , Masculino , Gravidez
19.
Proc Natl Acad Sci U S A ; 110(29): 11899-904, 2013 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-23818600

RESUMO

Classical hypotheses regarding the evolutionary origin of paired appendages propose transformation of precursor structures (gill arches and lateral fin folds) into paired fins. During development, gnathostome paired appendages form as outgrowths of body wall somatopleure, a tissue composed of somatic lateral plate mesoderm (LPM) and overlying ectoderm. In amniotes, LPM contributes connective tissue to abaxial musculature and forms ventrolateral dermis of the interlimb body wall. The phylogenetic distribution of this character is uncertain because lineage analyses of LPM have not been generated in anamniotes. We focus on the evolutionary history of the somatopleure to gain insight into the tissue context in which paired fins first appeared. Lampreys diverged from other vertebrates before the acquisition of paired fins and provide a model for investigating the preappendicular condition. We present vital dye fate maps that suggest the somatopleure is eliminated in lamprey as the LPM is separated from the ectoderm and sequestered to the coelomic linings during myotome extension. We also examine the distribution of postcranial mesoderm in catshark and axolotl. In contrast to lamprey, our findings support an LPM contribution to the trunk body wall of these taxa, which is similar to published data for amniotes. Collectively, these data lead us to hypothesize that a persistent somatopleure in the lateral body wall is a gnathostome synapomorphy, and the redistribution of LPM was a key step in generating the novel developmental module that ultimately produced paired fins. These embryological criteria can refocus arguments on paired fin origins and generate hypotheses testable by comparative studies on the source, sequence, and extent of genetic redeployment.


Assuntos
Nadadeiras de Animais/embriologia , Evolução Biológica , Derme/embriologia , Lampreias/embriologia , Mesoderma/embriologia , Ambystoma mexicanum/embriologia , Animais , Linhagem da Célula/fisiologia , Crioultramicrotomia , Proteínas de Fluorescência Verde/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Filogenia , Tubarões/embriologia
20.
J Invest Dermatol ; 133(10): 2332-2339, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23677168

RESUMO

Systematic ablation of previously identified dermal papilla (DP) signature genes in embryonic DP precursors will reveal their functional roles during hair follicle morphogenesis. In this study, we validate Enpp2/Autotaxin as one of the highest expressed signature genes in postnatal DP, and demonstrate specific expression of this lysophosphatidic acid (LPA)-generating enzyme in embryonic dermal condensates. We further identify dermal and epidermal expression of several LPA receptors, suggesting that LPA signaling could contribute to follicle morphogenesis in both mesenchymal and epithelial compartments. We then use the recently characterized Cre-expressing Tbx18 knock-in line to conditionally ablate Enpp2 in embryonic DP precursors. Despite efficient gene knockout in embryonic day 14.5 (E14.5) dermal condensates, morphogenesis proceeds regularly with normal numbers, lengths, and sizes of all hair follicle types, suggesting that Enpp2 is not required for hair follicle formation. To interrogate DP signature gene expression, we finally isolate control and Enpp2-null DP precursors and identify the expression and upregulation of LIPH, an alternative LPA-producing enzyme, suggesting that this gene could functionally compensate for the absence of Enpp2. We conclude that future coablation of both LPA-producing enzymes or of several LPA receptors may reveal the functional role of LPA signaling during hair follicle morphogenesis.


Assuntos
Derme/embriologia , Folículo Piloso/embriologia , Lipase/genética , Morfogênese/fisiologia , Diester Fosfórico Hidrolases/genética , Animais , Derme/citologia , Derme/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Folículo Piloso/citologia , Folículo Piloso/fisiologia , Lipase/metabolismo , Lisofosfolipídeos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Diester Fosfórico Hidrolases/metabolismo , Gravidez , Receptores de Ácidos Lisofosfatídicos/metabolismo , Transdução de Sinais/fisiologia , Proteínas com Domínio T/genética , Regulação para Cima/fisiologia
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