title: The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation.
abstract: The mouse placenta was unveiled as an important reservoir for hematopoietic stem cells (HSCs), yet the origin of placental HSCs was unknown. By tracking developing HSCs by expression of Runx1-lacZ and CD41, we have found that HSCs emerge in large vessels in the placenta. Analysis of Ncx1(-/-) embryos, which lack a heartbeat, verified that HSC development is initiated in the placental vasculature independent of blood flow. However, fewer CD41+ hematopoietic cells were found in Ncx1(-/-) placentas than in controls, implying that some HSCs/progenitors colonize the placenta via circulation and/or HSC emergence is compromised without blood flow. Importantly, placentas from Ncx1(-/-) embryos possessed equal potential to generate myelo-erythroid and B and T lymphoid cells upon explant culture, verifying intact multilineage hematopoietic potential, characteristic of developing HSCs. These data suggest that, in addition to providing a niche for a large pool of HSCs prior to liver colonization, the placenta is a true site of HSC generation.
authors: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Katrin E
authors: KE
authors: Rhodes
authors: Christos
authors: C
authors: Gekas
authors: Yanling
authors: Y
authors: Wang
authors: Christopher T
authors: CT
authors: Lux
authors: Cameron S
authors: CS
authors: Francis
authors: David N
authors: DN
authors: Chan
authors: Simon
authors: S
authors: Conway
authors: Stuart H
authors: SH
authors: Orkin
authors: Mervin C
authors: MC
authors: Yoder
authors: Hanna K A
authors: HK
authors: Mikkola
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000502:physiology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D005260:Female; D006411:Hematopoiesis, Extramedullary / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000098:blood supply* / Q000166:cytology; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C499849:NCX1 protein, mouse; D040201:Platelet Membrane Glycoprotein IIb; C493726:Runx1 protein, mouse; D019831:Sodium-Calcium Exchanger