RESUMO
Hair follicles are essential appendages of the mammalian skin, as hair performs vital functions of protection, thermoregulation and sensation. Hair follicles harbour exceptional regenerative abilities as they contain multiple somatic stem cell populations such as hair follicle stem cells (HFSCs) and melanocyte stem cells. Surrounding the stem cells and their progeny, diverse groups of cells and extracellular matrix proteins are organized to form a microenvironment (called 'niche') that serves to promote and maintain the optimal functioning of these stem cell populations. Recent studies have shed light on the intricate nature of the HFSC niche and its crucial role in regulating hair follicle regeneration. In this Review, we describe how the niche serves as a signalling hub, communicating, deciphering and integrating both local signals within the skin and systemic inputs from the body and environment to modulate HFSC activity. We delve into the recent advancements in identifying the cellular and molecular nature of the niche, providing a holistic perspective on its essential functions in hair follicle morphogenesis, regeneration and ageing.
Assuntos
Folículo Piloso , Nicho de Células-Tronco , Animais , Folículo Piloso/fisiologia , Cabelo , Células-Tronco/metabolismo , Envelhecimento , MamíferosRESUMO
In the skin, sympathetic nerves, arrector pili muscles, and hair follicles form a tri-lineage unit to cause piloerection or goosebumps. In this issue of Cell, Schwartz et al. report that, beyond goosebumps, muscle-anchored nerves form "synapse-like" connections with hair follicle stem cells to promote hair regeneration in response to cold.
Assuntos
Folículo Piloso , Piloereção , Cabelo , Músculo Liso , Células-TroncoRESUMO
Piloerection (goosebumps) requires concerted actions of the hair follicle, the arrector pili muscle (APM), and the sympathetic nerve, providing a model to study interactions across epithelium, mesenchyme, and nerves. Here, we show that APMs and sympathetic nerves form a dual-component niche to modulate hair follicle stem cell (HFSC) activity. Sympathetic nerves form synapse-like structures with HFSCs and regulate HFSCs through norepinephrine, whereas APMs maintain sympathetic innervation to HFSCs. Without norepinephrine signaling, HFSCs enter deep quiescence by down-regulating the cell cycle and metabolism while up-regulating quiescence regulators Foxp1 and Fgf18. During development, HFSC progeny secretes Sonic Hedgehog (SHH) to direct the formation of this APM-sympathetic nerve niche, which in turn controls hair follicle regeneration in adults. Our results reveal a reciprocal interdependence between a regenerative tissue and its niche at different stages and demonstrate sympathetic nerves can modulate stem cells through synapse-like connections and neurotransmitters to couple tissue production with demands.
Assuntos
Nervo Acessório/fisiologia , Folículo Piloso/citologia , Cabelo/crescimento & desenvolvimento , Proteínas Hedgehog/metabolismo , Norepinefrina/metabolismo , Transdução de Sinais/genética , Células-Tronco/metabolismo , Células-Tronco/fisiologia , Nervo Acessório/citologia , Animais , Ciclo Celular/genética , Temperatura Baixa , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Perfilação da Expressão Gênica , Cabelo/citologia , Cabelo/fisiologia , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piloereção , RNA-Seq , Receptores Adrenérgicos beta 2/deficiência , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor Smoothened/genética , Receptor Smoothened/metabolismo , Nicho de Células-Tronco , Células-Tronco/citologia , Sistema Nervoso Simpático/citologia , Sistema Nervoso Simpático/fisiologia , Sinapses/fisiologiaRESUMO
Maintenance of tissue homeostasis is dependent on the communication between stem cells and supporting cells in the same niche. Regulatory T cells (Treg cells) are emerging as a critical component of the stem-cell niche for supporting their differentiation. How Treg cells sense dynamic signals in this microenvironment and communicate with stem cells is mostly unknown. In the present study, by using hair follicles (HFs) to study Treg cell-stem cell crosstalk, we show an unrecognized function of the steroid hormone glucocorticoid in instructing skin-resident Treg cells to facilitate HF stem-cell (HFSC) activation and HF regeneration. Ablation of the glucocorticoid receptor (GR) in Treg cells blocks hair regeneration without affecting immune homeostasis. Mechanistically, GR and Foxp3 cooperate in Treg cells to induce transforming growth factor ß3 (TGF-ß3), which activates Smad2/3 in HFSCs and facilitates HFSC proliferation. The present study identifies crosstalk between Treg cells and HFSCs mediated by the GR-TGF-ß3 axis, highlighting a possible means of manipulating Treg cells to support tissue regeneration.
Assuntos
Glucocorticoides , Folículo Piloso , Glucocorticoides/metabolismo , Cabelo/metabolismo , Folículo Piloso/metabolismo , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta3/metabolismoRESUMO
Recent progresses in genomic technologies provide both opportunities and challenges to forensics.
Assuntos
Direito Penal , Criminosos , Impressões Digitais de DNA/tendências , Face/anatomia & histologia , Genômica/tendências , Olho , Marcadores Genéticos , Cabelo/anatomia & histologia , Humanos , Imageamento Tridimensional , Grupos Raciais/genética , Pigmentação da Pele/genética , Sequências de Repetição em TandemRESUMO
Although stem cells are subject to niche control, evidence is emerging that they also contribute to generating the niche through their offspring. Using the hair follicle as a model, Hsu at al. demonstrate that the transient-amplifying cells, downstream of stem cells and well-known cell producers, signal back to stem cells to maintain long-term regenerative capacity.
Assuntos
Folículo Piloso/citologia , Cabelo/citologia , Cabelo/fisiologia , Nicho de Células-Tronco , Células-Tronco/citologia , AnimaisRESUMO
Transit-amplifying cells (TACs) are an early intermediate in tissue regeneration. Here, using hair follicles (HFs) as a paradigm, we show that emerging TACs constitute a signaling center that orchestrates tissue growth. Whereas primed stem cells (SCs) generate TACs, quiescent SCs only proliferate after TACs form and begin expressing Sonic Hedgehog (SHH). TAC generation is independent of autocrine SHH, but the TAC pool wanes if they can't produce SHH. We trace this paradox to two direct actions of SHH: promoting quiescent-SC proliferation and regulating dermal factors that stoke TAC expansion. Ingrained within quiescent SCs' special sensitivity to SHH signaling is their high expression of GAS1. Without sufficient input from quiescent SCs, replenishment of primed SCs for the next hair cycle is compromised, delaying regeneration and eventually leading to regeneration failure. Our findings unveil TACs as transient but indispensable integrators of SC niche components and reveal an intriguing interdependency of primed and quiescent SC populations on tissue regeneration.
Assuntos
Folículo Piloso/citologia , Cabelo/citologia , Cabelo/fisiologia , Nicho de Células-Tronco , Células-Tronco/citologia , Animais , Proliferação de Células , Folículo Piloso/metabolismo , Proteínas Hedgehog/metabolismo , Camundongos , Regeneração , Transdução de Sinais , Células-Tronco/metabolismoRESUMO
Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.
Assuntos
Cabelo , Melanócitos , Transdução de Sinais , Animais , Camundongos , Cabelo/citologia , Cabelo/crescimento & desenvolvimento , Folículo Piloso/citologia , Folículo Piloso/fisiologia , Receptores de Hialuronatos/metabolismo , Melanócitos/citologia , Melanócitos/metabolismo , Nevo/metabolismo , Nevo/patologia , Osteopontina/metabolismo , Células-Tronco/citologiaRESUMO
Restoration of barrier-tissue integrity after injury is dependent on the function of immune cells and stem cells (SCs) residing in the tissue. In response to skin injury, hair-follicle stem cells (HFSCs), normally poised for hair generation, are recruited to the site of injury and differentiate into cells that repair damaged epithelium. We used a SC fate-mapping approach to examine the contribution of regulatory T (Treg) cells to epidermal-barrier repair after injury. Depletion of Treg cells impaired skin-barrier regeneration and was associated with a Th17 inflammatory response and failed HFSC differentiation. In this setting, damaged epithelial cells preferentially expressed the neutrophil chemoattractant CXCL5, and blockade of CXCL5 or neutrophil depletion restored barrier function and SC differentiation after epidermal injury. Thus, Treg-cell regulation of localized inflammation enables HFSC differentiation and, thereby, skin-barrier regeneration, with implications for the maintenance and repair of other barrier tissues.
Assuntos
Diferenciação Celular/fisiologia , Quimiocina CXCL5/metabolismo , Epiderme/metabolismo , Folículo Piloso/metabolismo , Interleucina-17/metabolismo , Regeneração/fisiologia , Linfócitos T Reguladores/metabolismo , Animais , Células Epidérmicas/metabolismo , Células Epiteliais/metabolismo , Cabelo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco/metabolismoRESUMO
An adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knockin mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify new biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans.
Assuntos
Evolução Biológica , Receptor Edar/genética , Glândulas Exócrinas/fisiologia , Cabelo/fisiologia , Camundongos , Modelos Animais , Adolescente , Adulto , Sequência de Aminoácidos , Animais , Evolução Molecular , Técnicas de Introdução de Genes , Pleiotropia Genética , Haplótipos , Humanos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Couro Cabeludo/fisiologia , Alinhamento de Sequência , Adulto JovemRESUMO
Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous.
Assuntos
Cães/genética , Genoma , Animais , Tamanho Corporal/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/veterinária , Cruzamento , Mapeamento Cromossômico , Modelos Animais de Doenças , Doenças do Cão/genética , Cães/anatomia & histologia , Cães/classificação , Extremidades/anatomia & histologia , Estudo de Associação Genômica Ampla , Glicoproteínas/genética , Glicoproteínas/fisiologia , Proteína HMGA2/genética , Proteína HMGA2/fisiologia , Cabelo/anatomia & histologia , Cardiopatias/genética , Cardiopatias/veterinária , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/veterinária , Osteossarcoma/genética , Osteossarcoma/veterinária , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Seleção Genética , Pele/anatomia & histologia , Crânio/anatomia & histologia , Proteína Smad2/genética , Proteína Smad2/fisiologia , Especificidade da Espécie , Cauda/anatomia & histologiaRESUMO
Natural species have developed complex nanostructures in a hierarchical pattern to control the absorption, reflection, or transmission of desired solar and infrared wavelengths. This bio-inspired structure is a promising method to manipulating solar energy and thermal management. In particular, human hair is used in this article to highlight the optothermal properties of bio-inspired structures. This study investigated how melanin, an effective solar absorber, and the structural morphology of aligned domains of keratin polymer chains, leading to a significant increase in solar path length, which effectively scatter and absorb solar radiation across the hair structure, as well as enhance thermal ramifications from solar absorption by fitting its radiative wavelength to atmospheric transmittance for high-yield radiative cooling with realistic human body thermal emission.
Assuntos
Energia Solar , Humanos , Transição de Fase , Temperatura Baixa , Citoesqueleto , CabeloRESUMO
BACKGROUND: Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking. METHODS: We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum. Hair samples were collected quarterly for objective assessment of doxycycline use. RESULTS: A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae-positive isolates were resistant to doxycycline. CONCLUSIONS: Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.).
Assuntos
Anti-Infecciosos , Infecções por Chlamydia , Doxiciclina , Gonorreia , Profilaxia Pré-Exposição , Sífilis , Feminino , Humanos , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/prevenção & controle , Chlamydia trachomatis , Doxiciclina/administração & dosagem , Doxiciclina/efeitos adversos , Doxiciclina/análise , Doxiciclina/uso terapêutico , Infecções por HIV/prevenção & controle , Quênia/epidemiologia , Neisseria gonorrhoeae , Profilaxia Pré-Exposição/métodos , Infecções Sexualmente Transmissíveis/prevenção & controle , Sexo sem Proteção , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/análise , Anti-Infecciosos/uso terapêutico , Adolescente , Adulto Jovem , Adulto , Gonorreia/microbiologia , Gonorreia/prevenção & controle , Treponema pallidum , Sífilis/microbiologia , Sífilis/prevenção & controle , Monitoramento de Medicamentos/métodos , Cabelo/químicaRESUMO
Tissue interactions are essential for guiding organ development and regeneration. Hair follicle formation relies on inductive signalling between two tissues, the embryonic surface epithelium and the adjacent mesenchyme. Although previous research has highlighted the hair-inducing potential of the mesenchymal component of the hair follicle - the dermal papilla and its precursor, the dermal condensate - the source and nature of the primary inductive signal before dermal condensate formation have remained elusive. Here, we performed epithelial-mesenchymal tissue recombination experiments using hair-forming back skin and glabrous plantar skin from mouse embryos to unveil that the back skin mesenchyme is inductive even before dermal condensate formation. Moreover, the naïve, unpatterned mesenchyme was sufficient to trigger hair follicle formation even in the oral epithelium. Building on previous knowledge, we explored the hair-inductive ability of the Wnt agonist R-spondin 1 and a Bmp receptor inhibitor in embryonic skin explants. Although R-spondin 1 instigated precocious placode-specific transcriptional responses, it was insufficient for hair follicle induction, either alone or in combination with Bmp receptor inhibition. Our findings pave the way for identifying the hair follicle-inducing cue.
Assuntos
Folículo Piloso , Cabelo , Camundongos , Animais , Folículo Piloso/fisiologia , Pele , Mesoderma/fisiologia , Receptores de Proteínas Morfogenéticas ÓsseasRESUMO
Innocuous touch of the skin is detected by distinct populations of neurons, the low-threshold mechanoreceptors (LTMRs), which are classified as Aß-, Aδ-, and C-LTMRs. Here, we report genetic labeling of LTMR subtypes and visualization of their relative patterns of axonal endings in hairy skin and the spinal cord. We found that each of the three major hair follicle types of trunk hairy skin (guard, awl/auchene, and zigzag hairs) is innervated by a unique and invariant combination of LTMRs; thus, each hair follicle type is a functionally distinct mechanosensory end organ. Moreover, the central projections of Aß-, Aδ-, and C-LTMRs that innervate the same or adjacent hair follicles form narrow LTMR columns in the dorsal horn. These findings support a model of mechanosensation in which the activities of Aß-, Aδ-, and C-LTMRs are integrated within dorsal horn LTMR columns and processed into outputs that underlie the perception of myriad touch sensations.
Assuntos
Cabelo/fisiologia , Mecanorreceptores/fisiologia , Fenômenos Fisiológicos da Pele , Pele/inervação , Animais , Axônios/fisiologia , Camundongos , Neurônios/fisiologia , Limiar Sensorial , Pele/citologia , Medula Espinal/fisiologiaRESUMO
Melanocyte stem cells (McSCs) intimately interact with epithelial stem cells (EpSCs) in the hair follicle bulge and secondary hair germ (sHG). Together, they undergo activation and differentiation to regenerate pigmented hair. However, the mechanisms behind this coordinated stem cell behavior have not been elucidated. Here, we identified Wnt signaling as a key pathway that couples the behavior of the two stem cells. EpSCs and McSCs coordinately activate Wnt signaling at the onset of hair follicle regeneration within the sHG. Using genetic mouse models that specifically target either EpSCs or McSCs, we show that Wnt activation in McSCs drives their differentiation into pigment-producing melanocytes, while EpSC Wnt signaling not only dictates hair follicle formation but also regulates McSC proliferation during hair regeneration. Our data define a role for Wnt signaling in the regulation of McSCs and also illustrate a mechanism for regeneration of complex organs through collaboration between heterotypic stem cell populations.
Assuntos
Células Epiteliais/citologia , Cabelo/fisiologia , Melanócitos/citologia , Pigmentação , Fenômenos Fisiológicos da Pele , Células-Tronco/citologia , Proteínas Wnt/metabolismo , Animais , Diferenciação Celular , Cabelo/citologia , Doenças do Cabelo/metabolismo , Doenças do Cabelo/patologia , Folículo Piloso/citologia , Humanos , Camundongos , Regeneração , Transdução de Sinais , Pele/citologia , beta Catenina/metabolismoRESUMO
The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain1,2. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met3-9. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor ß (TGFß) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.
Assuntos
Cabelo/citologia , Cabelo/crescimento & desenvolvimento , Organoides/citologia , Células-Tronco Pluripotentes/citologia , Pele/citologia , Animais , Ectoderma/citologia , Feminino , Cabelo/transplante , Cor de Cabelo , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/inervação , Folículo Piloso/transplante , Cabeça , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Organoides/crescimento & desenvolvimento , Organoides/inervação , Organoides/transplante , RNA-Seq , Análise de Célula Única , Pele/crescimento & desenvolvimento , Pele/inervação , Transplante de PeleRESUMO
Humans are unique among mammals in having a functionally naked body with a hair-covered scalp. Scalp hair is exceptionally variable across populations within Homo sapiens. Neither the function of human scalp hair nor the consequences of variation in its morphology have been studied within an evolutionary framework. A thermoregulatory role for human scalp hair has been previously suggested. Here, we present experimental evidence on the potential evolutionary function of human scalp hair and variation in its morphology. Using a thermal manikin and human hair wigs at different wind speeds in a temperature and humidity-controlled environment, with and without simulated solar radiation, we collected data on the convective, radiative, and evaporative heat fluxes to and from the scalp in relation to properties of a range of hair morphologies, as well as a naked scalp. We find evidence for a significant reduction in solar radiation influx to the scalp in the presence of hair. Maximal evaporative heat loss potential from the scalp is reduced by the presence of hair, but the amount of sweat required on the scalp to balance the incoming solar heat (i.e., zero heat gain) is reduced in the presence of hair. Particularly, we find that hair that is more tightly curled offers increased protection against heat gain from solar radiation.
Assuntos
Regulação da Temperatura Corporal , Cabelo , Couro Cabeludo , Cabelo/anatomia & histologia , Cabelo/fisiologia , Regulação da Temperatura Corporal/fisiologia , Humanos , Evolução Biológica , Água , Vento , Energia SolarRESUMO
Stiffness and actomyosin contractility are intrinsic mechanical properties of animal cells required for the shaping of tissues. However, whether tissue stem cells (SCs) and progenitors located within SC niche have different mechanical properties that modulate their size and function remains unclear. Here, we show that hair follicle SCs in the bulge are stiff with high actomyosin contractility and resistant to size change, whereas hair germ (HG) progenitors are soft and periodically enlarge and contract during quiescence. During activation of hair follicle growth, HGs reduce contraction and more frequently enlarge, a process that is associated with weakening of the actomyosin network, nuclear YAP accumulation, and cell cycle reentry. Induction of miR-205, a novel regulator of the actomyosin cytoskeleton, reduces actomyosin contractility and activates hair regeneration in young and old mice. This study reveals the control of tissue SC size and activities by spatiotemporally compartmentalized mechanical properties and demonstrates the possibility to stimulate tissue regeneration by fine-tuning cell mechanics.