The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation.
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.
Rhodes
Katrin E
KE
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Gekas
Christos
C
Wang
Yanling
Y
Lux
Christopher T
CT
Francis
Cameron S
CS
Chan
David N
DN
Conway
Simon
S
Orkin
Stuart H
SH
Yoder
Mervin C
MC
Mikkola
Hanna K A
HK
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
D050676:Core Binding Factor Alpha 2 Subunit; C499849:NCX1 protein, mouse; D040201:Platelet Membrane Glycoprotein IIb; C493726:Runx1 protein, mouse; D019831:Sodium-Calcium Exchanger