The Emergence of Hematopoietic Stem Cells Is Initiated in the Placental Vasculature in the Absence of Circulation

Katrin E. Rhodes, Christos Gekas, Yanling Wang, Christopher T. Lux, Cameron S. Francis, David N. Chan, Simon Conway, Stuart H. Orkin, Mervin C. Yoder, Hanna K.A. Mikkola

Research output: Contribution to journalArticle

204 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)252-263
Number of pages12
JournalCell Stem Cell
Volume2
Issue number3
DOIs
StatePublished - Mar 6 2008

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Keywords

  • STEMCELL

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Rhodes, K. E., Gekas, C., Wang, Y., Lux, C. T., Francis, C. S., Chan, D. N., Conway, S., Orkin, S. H., Yoder, M. C., & Mikkola, H. K. A. (2008). The Emergence of Hematopoietic Stem Cells Is Initiated in the Placental Vasculature in the Absence of Circulation. Cell Stem Cell, 2(3), 252-263. https://doi.org/10.1016/j.stem.2008.01.001