title: hESC Differentiation toward an Autonomic Neuronal Cell Fate Depends on Distinct Cues from the Co-Patterning Vasculature.
abstract: 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 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 distinct molecular cues from VSMCs and ECs, providing a model for how other developing lineages might coordinate their co-patterning.
authors.affiliation: Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA; Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Lisette M
authors.initials: LM
authors.lastname: Acevedo
authors.affiliation: Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA; Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Lindquist
authors.affiliation: Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
authors.forename: Breda M
authors.initials: BM
authors.lastname: Walsh
authors.affiliation: Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
authors.forename: Peik
authors.initials: P
authors.lastname: Sia
authors.affiliation: Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Flavio
authors.initials: F
authors.lastname: Cimadamore
authors.affiliation: Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Chen
authors.affiliation: Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Denzel
authors.affiliation: Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA.
authors.forename: Cameron D
authors.initials: CD
authors.lastname: Pernia
authors.affiliation: Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ranscht
authors.affiliation: Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Alexey
authors.initials: A
authors.lastname: Terskikh
authors.affiliation: Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: esnyder@sanfordburnham.org.
authors.forename: Evan Y
authors.initials: EY
authors.lastname: Snyder
authors.affiliation: Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: dcheresh@ucsd.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Cheresh
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D004475:Ectoderm / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D064531:Peripherins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D015820:Cadherins; C099972:H-cadherin; D020030:Nitric Oxide Donors; C578994:PRPH protein, human; D064531:Peripherins; D034741:RNA, Small Interfering; D014404:Tubulin; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III