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1.
Cell ; 187(13): 3194-3219, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38906095

RESUMEN

Developing functional organs from stem cells remains a challenging goal in regenerative medicine. Existing methodologies, such as tissue engineering, bioprinting, and organoids, only offer partial solutions. This perspective focuses on two promising approaches emerging for engineering human organs from stem cells: stem cell-based embryo models and interspecies organogenesis. Both approaches exploit the premise of guiding stem cells to mimic natural development. We begin by summarizing what is known about early human development as a blueprint for recapitulating organogenesis in both embryo models and interspecies chimeras. The latest advances in both fields are discussed before highlighting the technological and knowledge gaps to be addressed before the goal of developing human organs could be achieved using the two approaches. We conclude by discussing challenges facing embryo modeling and interspecies organogenesis and outlining future prospects for advancing both fields toward the generation of human tissues and organs for basic research and translational applications.


Asunto(s)
Quimera , Organogénesis , Animales , Humanos , Quimera/embriología , Implantación del Embrión , Embrión de Mamíferos/citología , Desarrollo Embrionario , Células Madre Embrionarias , Modelos Biológicos , Organoides , Medicina Regenerativa , Ingeniería de Tejidos/métodos
2.
Cell ; 187(9): 2129-2142.e17, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38670071

RESUMEN

Interspecies blastocyst complementation (IBC) provides a unique platform to study development and holds the potential to overcome worldwide organ shortages. Despite recent successes, brain tissue has not been achieved through IBC. Here, we developed an optimized IBC strategy based on C-CRISPR, which facilitated rapid screening of candidate genes and identified that Hesx1 deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneic rat forebrain tissues in adult mice were structurally and functionally intact. Cross-species comparative analyses revealed that rat forebrain tissues developed at the same pace as the mouse host but maintained rat-like transcriptome profiles. The chimeric rate of rat cells gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late pre-natal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRISPR-based IBC strategy holds great potential to broaden the study and application of interspecies organogenesis.


Asunto(s)
Prosencéfalo , Animales , Prosencéfalo/metabolismo , Prosencéfalo/embriología , Ratones , Ratas , Blastocisto/metabolismo , Femenino , Sistemas CRISPR-Cas/genética , Transcriptoma , Organogénesis , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Masculino , Ratones Endogámicos C57BL
3.
Cell ; 186(10): 2092-2110.e23, 2023 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-37172563

RESUMEN

The third and fourth weeks of gestation in primates are marked by several developmental milestones, including gastrulation and the formation of organ primordia. However, our understanding of this period is limited due to restricted access to in vivo embryos. To address this gap, we developed an embedded 3D culture system that allows for the extended ex utero culture of cynomolgus monkey embryos for up to 25 days post-fertilization. Morphological, histological, and single-cell RNA-sequencing analyses demonstrate that ex utero cultured monkey embryos largely recapitulated key events of in vivo development. With this platform, we were able to delineate lineage trajectories and genetic programs involved in neural induction, lateral plate mesoderm differentiation, yolk sac hematopoiesis, primitive gut, and primordial germ-cell-like cell development in monkeys. Our embedded 3D culture system provides a robust and reproducible platform for growing monkey embryos from blastocysts to early organogenesis and studying primate embryogenesis ex utero.


Asunto(s)
Embrión de Mamíferos , Desarrollo Embrionario , Animales , Macaca fascicularis , Blastocisto , Organogénesis , Primates
4.
Cell ; 186(18): 3776-3792.e16, 2023 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-37478861

RESUMEN

In vitro stem cell models that replicate human gastrulation have been generated, but they lack the essential extraembryonic cells needed for embryonic development, morphogenesis, and patterning. Here, we describe a robust and efficient method that prompts human extended pluripotent stem cells to self-organize into embryo-like structures, termed peri-gastruloids, which encompass both embryonic (epiblast) and extraembryonic (hypoblast) tissues. Although peri-gastruloids are not viable due to the exclusion of trophoblasts, they recapitulate critical stages of human peri-gastrulation development, such as forming amniotic and yolk sac cavities, developing bilaminar and trilaminar embryonic discs, specifying primordial germ cells, initiating gastrulation, and undergoing early neurulation and organogenesis. Single-cell RNA-sequencing unveiled transcriptomic similarities between advanced human peri-gastruloids and primary peri-gastrulation cell types found in humans and non-human primates. This peri-gastruloid platform allows for further exploration beyond gastrulation and may potentially aid in the development of human fetal tissues for use in regenerative medicine.


Asunto(s)
Implantación del Embrión , Gastrulación , Células Madre Pluripotentes , Animales , Femenino , Humanos , Embarazo , Diferenciación Celular , Embrión de Mamíferos , Desarrollo Embrionario , Organogénesis , Células Madre Pluripotentes/metabolismo , Primates
5.
Cell ; 186(6): 1212-1229.e21, 2023 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-36827974

RESUMEN

Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments.


Asunto(s)
Mitocondrias , Organogénesis , Animales , Femenino , Humanos , Ratones , Embarazo , Linaje de la Célula , ADN Mitocondrial/genética , Mitocondrias/metabolismo , Enfermedades Mitocondriales , Especificidad de Órganos , Desarrollo Embrionario , Embrión de Mamíferos/citología , Embrión de Mamíferos/metabolismo
6.
Annu Rev Immunol ; 33: 715-45, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25861980

RESUMEN

Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.


Asunto(s)
Inflamación/inmunología , Inflamación/metabolismo , Tejido Linfoide/inmunología , Tejido Linfoide/metabolismo , Células del Estroma/inmunología , Células del Estroma/metabolismo , Animales , Comunicación Celular , Enfermedad Crónica , Humanos , Inflamación/patología , Organogénesis/inmunología , Fenotipo
7.
Cell ; 185(10): 1625-1627, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35561663

RESUMEN

The generation of spatial transcriptomes of whole embryo has been limited in scale and resolution due to various technological restrictions. In this issue of Cell, Chen et al. introduce a DNA nanoball-based sample-capture technology for spatial transcriptome analysis to generate a molecular atlas of mouse organogenesis at single-cell resolution.


Asunto(s)
Organogénesis , Transcriptoma , Animales , Embrión de Mamíferos , Perfilación de la Expresión Génica , Ratones , Organogénesis/genética , Análisis de la Célula Individual
8.
Cell ; 185(10): 1777-1792.e21, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35512705

RESUMEN

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.


Asunto(s)
Organogénesis , Transcriptoma , Animales , ADN/genética , Embrión de Mamíferos , Femenino , Perfilación de la Expresión Génica/métodos , Mamíferos/genética , Ratones , Organogénesis/genética , Embarazo , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Transcriptoma/genética
9.
Cell ; 185(25): 4841-4860.e25, 2022 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-36493756

RESUMEN

We present a multiomic cell atlas of human lung development that combines single-cell RNA and ATAC sequencing, high-throughput spatial transcriptomics, and single-cell imaging. Coupling single-cell methods with spatial analysis has allowed a comprehensive cellular survey of the epithelial, mesenchymal, endothelial, and erythrocyte/leukocyte compartments from 5-22 post-conception weeks. We identify previously uncharacterized cell states in all compartments. These include developmental-specific secretory progenitors and a subtype of neuroendocrine cell related to human small cell lung cancer. Our datasets are available through our web interface (https://lungcellatlas.org). To illustrate its general utility, we use our cell atlas to generate predictions about cell-cell signaling and transcription factor hierarchies which we rigorously test using organoid models.


Asunto(s)
Feto , Pulmón , Humanos , Diferenciación Celular , Perfilación de la Expresión Génica , Pulmón/citología , Organogénesis , Organoides , Atlas como Asunto , Feto/citología
10.
Cell ; 185(1): 95-112.e18, 2022 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-34995520

RESUMEN

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized "pattern-block" correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.


Asunto(s)
Dermatoglifia , Dedos/crecimiento & desarrollo , Organogénesis/genética , Polimorfismo de Nucleótido Simple , Dedos del Pie/crecimiento & desarrollo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Pueblo Asiatico/genética , Tipificación del Cuerpo/genética , Niño , Estudios de Cohortes , Femenino , Miembro Anterior/crecimiento & desarrollo , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Proteína del Locus del Complejo MDS1 y EV11/genética , Masculino , Ratones , Persona de Mediana Edad , Adulto Joven
11.
Cell ; 184(3): 723-740.e21, 2021 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-33508230

RESUMEN

Elucidating the regulatory mechanisms of human brain evolution is essential to understanding human cognition and mental disorders. We generated multi-omics profiles and constructed a high-resolution map of 3D genome architecture of rhesus macaque during corticogenesis. By comparing the 3D genomes of human, macaque, and mouse brains, we identified many human-specific chromatin structure changes, including 499 topologically associating domains (TADs) and 1,266 chromatin loops. The human-specific loops are significantly enriched in enhancer-enhancer interactions, and the regulated genes show human-specific expression changes in the subplate, a transient zone of the developing brain critical for neural circuit formation and plasticity. Notably, many human-specific sequence changes are located in the human-specific TAD boundaries and loop anchors, which may generate new transcription factor binding sites and chromatin structures in human. Collectively, the presented data highlight the value of comparative 3D genome analyses in dissecting the regulatory mechanisms of brain development and evolution.


Asunto(s)
Encéfalo/embriología , Evolución Molecular , Feto/embriología , Genoma , Organogénesis/genética , Animales , Secuencia de Bases , Cromatina/metabolismo , Elementos Transponibles de ADN/genética , Elementos de Facilitación Genéticos/genética , Regulación del Desarrollo de la Expresión Génica , Humanos , Macaca mulatta , Ratones , Especificidad de la Especie , Sintenía/genética , Factores de Transcripción/metabolismo
12.
Cell ; 184(12): 3299-3317.e22, 2021 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-34019794

RESUMEN

Organoids capable of forming tissue-like structures have transformed our ability to model human development and disease. With the notable exception of the human heart, lineage-specific self-organizing organoids have been reported for all major organs. Here, we established self-organizing cardioids from human pluripotent stem cells that intrinsically specify, pattern, and morph into chamber-like structures containing a cavity. Cardioid complexity can be controlled by signaling that instructs the separation of cardiomyocyte and endothelial layers and by directing epicardial spreading, inward migration, and differentiation. We find that cavity morphogenesis is governed by a mesodermal WNT-BMP signaling axis and requires its target HAND1, a transcription factor linked to developmental heart chamber defects. Upon cryoinjury, cardioids initiated a cell-type-dependent accumulation of extracellular matrix, an early hallmark of both regeneration and heart disease. Thus, human cardioids represent a powerful platform to mechanistically dissect self-organization, congenital heart defects and serve as a foundation for future translational research.


Asunto(s)
Corazón/embriología , Organogénesis , Organoides/embriología , Activinas/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Calcio/metabolismo , Línea Celular , Linaje de la Célula , Pollos , Células Endoteliales/citología , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Fibroblastos/citología , Proteína Homeótica Nkx-2.5/metabolismo , Humanos , Masculino , Mesodermo/embriología , Modelos Biológicos , Miocardio/metabolismo , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Wnt/metabolismo
13.
Cell ; 175(3): 859-876.e33, 2018 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-30318151

RESUMEN

The mouse embryo has long been central to the study of mammalian development; however, elucidating the cell behaviors governing gastrulation and the formation of tissues and organs remains a fundamental challenge. A major obstacle is the lack of live imaging and image analysis technologies capable of systematically following cellular dynamics across the developing embryo. We developed a light-sheet microscope that adapts itself to the dramatic changes in size, shape, and optical properties of the post-implantation mouse embryo and captures its development from gastrulation to early organogenesis at the cellular level. We furthermore developed a computational framework for reconstructing long-term cell tracks, cell divisions, dynamic fate maps, and maps of tissue morphogenesis across the entire embryo. By jointly analyzing cellular dynamics in multiple embryos registered in space and time, we built a dynamic atlas of post-implantation mouse development that, together with our microscopy and computational methods, is provided as a resource. VIDEO ABSTRACT.


Asunto(s)
Linaje de la Célula , Gastrulación , Organogénesis , Análisis de la Célula Individual/métodos , Animales , Ratones , Ratones Endogámicos C57BL , Modelos Estadísticos , Imagen Óptica/métodos
14.
Immunity ; 56(6): 1204-1219.e8, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37160119

RESUMEN

During development, lymph node (LN) initiation is coordinated by lymphoid tissue organizer (LTo) cells that attract lymphoid tissue inducer (LTi) cells at strategic positions within the embryo. The identity and function of LTo cells during the initial attraction of LTi cells remain poorly understood. Using lineage tracing, we demonstrated that a subset of Osr1-expressing cells was mesenchymal LTo progenitors. By investigating the heterogeneity of Osr1+ cells, we uncovered distinct mesenchymal LTo signatures at diverse anatomical locations, identifying a common progenitor of mesenchymal LTos and LN-associated adipose tissue. Osr1 was essential for LN initiation, driving the commitment of mesenchymal LTo cells independent of neural retinoic acid, and for LN-associated lymphatic vasculature assembly. The combined action of chemokines CXCL13 and CCL21 was required for LN initiation. Our results redefine the role and identity of mesenchymal organizer cells and unify current views by proposing a model of cooperative cell function in LN initiation.


Asunto(s)
Organogénesis , Factores de Transcripción , Diferenciación Celular , Ganglios Linfáticos , Tejido Linfoide
15.
Cell ; 169(1): 161-173.e12, 2017 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-28340341

RESUMEN

Generating a precise cellular and molecular cartography of the human embryo is essential to our understanding of the mechanisms of organogenesis in normal and pathological conditions. Here, we have combined whole-mount immunostaining, 3DISCO clearing, and light-sheet imaging to start building a 3D cellular map of the human development during the first trimester of gestation. We provide high-resolution 3D images of the developing peripheral nervous, muscular, vascular, cardiopulmonary, and urogenital systems. We found that the adult-like pattern of skin innervation is established before the end of the first trimester, showing important intra- and inter-individual variations in nerve branches. We also present evidence for a differential vascularization of the male and female genital tracts concomitant with sex determination. This work paves the way for a cellular and molecular reference atlas of human cells, which will be of paramount importance to understanding human development in health and disease. PAPERCLIP.


Asunto(s)
Embrión de Mamíferos/citología , Feto/citología , Desarrollo Humano , Imagenología Tridimensional/métodos , Inmunohistoquímica/métodos , Microscopía/métodos , Desarrollo Embrionario , Humanos , Organogénesis , Sistema Nervioso Periférico/citología , Sistema Nervioso Periférico/crecimiento & desarrollo
16.
Annu Rev Cell Dev Biol ; 34: 427-450, 2018 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-30125139

RESUMEN

The nephron is a multifunctional filtration device equipped with an array of sophisticated sensors. For appropriate physiological function in the human and mouse, nephrons must be stereotypically arrayed in large numbers, and this essential structural property that defines the kidney is determined during its fetal development. This review explores the process of nephron determination in the fetal kidney, providing an overview of the foundational literature in the field as well as exploring new developments in this dynamic research area. Mechanisms that ensure that a large number of nephrons can be formed from a small initial number of progenitor cells are central to this process, and the question of how the nephron progenitor cell population balances epithelial differentiation with renewal in the progenitor state is a subject of particular interest. Key growth factor signaling pathways and transcription factor networks are discussed.


Asunto(s)
Diferenciación Celular/genética , Desarrollo Fetal/genética , Riñón/crecimiento & desarrollo , Nefronas/crecimiento & desarrollo , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Riñón/metabolismo , Nefronas/metabolismo , Organogénesis/genética , Transducción de Señal/genética , Células Madre/citología
17.
Cell ; 164(5): 999-1014, 2016 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-26875865

RESUMEN

Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and the zinc finger TF GATA4 coordinately controlling cardiac gene expression, differentiation, and morphogenesis. Interdependent binding serves not only to co-regulate gene expression but also to prevent TFs from distributing to ectopic loci and activate lineage-inappropriate genes. We define preferential motif arrangements for TBX5 and NKX2-5 cooperative binding sites, supported at the atomic level by their co-crystal structure bound to DNA, revealing a direct interaction between the two factors and induced DNA bending. Complex interdependent binding mechanisms reveal tightly regulated TF genomic distribution and define a combinatorial logic for heterotypic TF regulation of differentiation.


Asunto(s)
Factor de Transcripción GATA4/metabolismo , Proteínas de Homeodominio/metabolismo , Miocardio/citología , Organogénesis , Proteínas de Dominio T Box/metabolismo , Factores de Transcripción/metabolismo , Animales , Diferenciación Celular , Cristalografía por Rayos X , Embrión de Mamíferos/metabolismo , Proteína Homeótica Nkx-2.5 , Proteínas de Homeodominio/genética , Ratones , Ratones Transgénicos , Modelos Moleculares , Miocardio/metabolismo , Regiones Promotoras Genéticas , Dominios y Motivos de Interacción de Proteínas , Proteínas de Dominio T Box/genética , Factores de Transcripción/genética
18.
Annu Rev Cell Dev Biol ; 33: 203-217, 2017 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-28806099

RESUMEN

As chimeras transform from beasts of Greek mythology into tools of contemporary bioscience, secrets of developmental biology and evolutionary divergence are being revealed. Recent advances in stem cell biology and interspecies chimerism have generated new models with extensive basic and translational applications, including generation of transplantable, patient-specific organs.


Asunto(s)
Quimera/metabolismo , Mamíferos/metabolismo , Animales , Humanos , Organogénesis , Especificidad de la Especie
19.
Genes Dev ; 37(15-16): 675-677, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37673460

RESUMEN

Specialized enzymes add methyl groups to the nitrogens of the amino acid histidine, altering the chemical properties of its imidazole ring and, in turn, the function of the modified (poly)peptide. In this issue of Genes & Development, Shimazu and colleagues (pp. 724-742) make the remarkable discovery that CARNMT1 acts as a dual-specificity histidine methyltransferase, modifying both the small-molecule dipeptide carnosine and a set of proteins, predominantly within RNA-binding C3H zinc finger (C3H ZF) motifs. As a result, CARNMT1 modulates the activity of its protein targets to affect RNA processing and metabolism, ultimately contributing an essential function during mammalian development.


Asunto(s)
Aminoácidos , Histidina , Animales , Metilación , Metiltransferasas , Organogénesis , Mamíferos
20.
Immunity ; 54(5): 1022-1036.e8, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33932356

RESUMEN

The sympathetic nervous system is composed of an endocrine arm, regulating blood adrenaline and noradrenaline, and a local arm, a network of fibers innervating immune organs. Here, we investigated the impact of the local arm of the SNS in an inflammatory response in the colon. Intra-rectal insertion of an optogenetic probe in mice engineered to express channelrhodopsin-2 in tyrosine hydroxylase cells activated colonic sympathetic fibers. In contrast to systemic application of noradrenaline, local activation of sympathetic fibers attenuated experimental colitis and reduced immune cell abundance. Gene expression profiling showed decreased endothelial expression of the adhesion molecule MAdCAM-1 upon optogenetic stimulation; this decrease was sensitive to adrenergic blockers and 6-hydroxydopamine. Antibody blockade of MAdCAM-1 abrogated the optogenetic effect on immune cell extravasation into the colon and the pathology. Thus, sympathetic fibers control colonic inflammation by regulating immune cell extravasation from circulation, a mechanism likely relevant in multiple organs.


Asunto(s)
Colitis/inmunología , Colon/inmunología , Colon/inervación , Organogénesis/inmunología , Sistema Nervioso Simpático/inmunología , Animales , Molécula 1 de Adhesión Intercelular/inmunología , Ratones , Ratones Endogámicos C57BL , Optogenética/métodos
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