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Nat Genet ; 53(5): 694-706, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33833454

RESUMEN

Characterization of the progression of cellular states during human embryogenesis can provide insights into the origin of pediatric diseases. We examined the transcriptional states of neural crest- and mesoderm-derived lineages differentiating into adrenal glands, kidneys, endothelium and hematopoietic tissue between post-conception weeks 6 and 14 of human development. Our results reveal transitions connecting the intermediate mesoderm and progenitors of organ primordia, the hematopoietic system and endothelial subtypes. Unexpectedly, by using a combination of single-cell transcriptomics and lineage tracing, we found that intra-adrenal sympathoblasts at that stage are directly derived from nerve-associated Schwann cell precursors, similarly to local chromaffin cells, whereas the majority of extra-adrenal sympathoblasts arise from the migratory neural crest. In humans, this process persists during several weeks of development within the large intra-adrenal ganglia-like structures, which may also serve as reservoirs of originating cells in neuroblastoma.


Asunto(s)
Linaje de la Célula , Embrión de Mamíferos/metabolismo , Neuroblastoma/embriología , Neuroblastoma/genética , Análisis de la Célula Individual , Sistema Simpatoadrenal/embriología , Transcriptoma/genética , Animales , Células Cromafines/metabolismo , Células Cromafines/patología , Análisis por Conglomerados , Desarrollo Embrionario , Regulación del Desarrollo de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Lactante , Ratones , Células-Madre Neurales/metabolismo , Neuroblastoma/patología , Células de Schwann/metabolismo , Células de Schwann/patología , Microambiente Tumoral
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