HESC DIFFERENTIATION TOWARD AN AUTONOMIC NEURONAL CELL FATE DEPENDS ON DISTINCT CUES FROM THE CO-PATTERNING VASCULATURE

hESC Differentiation toward an Autonomic Neuronal Cell Fate Depends on Distinct Cues from the Co-Patterning Vasculature

hESC Differentiation toward an Autonomic Neuronal Cell Fate Depends on Distinct Cues from the Co-Patterning Vasculature

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To gain insight into the cellular and molecular cues that promote neurovascular co-patterning at the earliest stages of human embryogenesis, we developed a human embryonic stem cell model to mimic the developing epiblast.Contact of ectoderm-derived neural cells with mesoderm-derived vasculature is initiated via the neural crest (NC), not the neural tube (NT).Neurovascular co-patterning then ensues with specification read more of NC toward an autonomic fate requiring vascular endothelial cell (EC)-secreted nitric oxide (NO) and direct contact with vascular smooth muscle cells (VSMCs) via T-cadherin-mediated homotypic interactions.Once a neurovascular template has been established, NT-derived central neurons then align themselves with the vasculature.Our findings reveal that, in early human development, the autonomic nervous system forms in response to turbo air m3f72-3-n distinct molecular cues from VSMCs and ECs, providing a model for how other developing lineages might coordinate their co-patterning.

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