Trophoblasts Regulate the Placental Hematopoietic Niche through PDGF-B Signaling

Akanksha Chhabra, Andrew J. Lechner, Masaya Ueno, Asha Acharya, Ben Van Handel, Yanling Wang, M. Luisa Iruela-Arispe, Michelle D. Tallquist, Hanna K A Mikkola

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

The placenta is a hematopoietic organ that supports hematopoietic stem/progenitor cell (HSPC) generation and expansion without promoting differentiation. We identified PDGF-B signaling in trophoblasts as a key component of the unique placental hematopoietic microenvironment that protects HSPCs from premature differentiation. Loss of PDGF-B or its receptor, PDGFRβ, induced definitive erythropoiesis in placental labyrinth vasculature. This was evidenced by accumulation of CFU-Es and actively proliferating definitive erythroblasts that clustered around central macrophages, highly reminiscent of erythropoiesis in the fetal liver. Ectopic erythropoiesis was not due to a requirement of PDGF-B signaling in hematopoietic cells but rather in placental trophoblasts, which upregulated Epo in the absence of PDGF-B signaling. Furthermore, overexpression of hEPO specifically in the trophoblasts in vivo was sufficient to convert the placenta into an erythropoietic organ. These data provide genetic evidence of a signaling pathway that is required to restrict erythroid differentiation to specific anatomical niches during development. Video Abstract: The placenta is an important embryonic niche for hematopoietic stem/progenitor cells (HSPCs). Chhabra et al. find that PDGF signaling suppresses Epo production by placental trophoblasts and thereby attenuates placental erythropoiesis. Thus, PDGF signaling determines niche characteristics that in turn influence resident HSPCs to control the cell-type specificity of HSPC output.

Original languageEnglish (US)
Pages (from-to)651-659
Number of pages9
JournalDevelopmental Cell
Volume22
Issue number3
DOIs
StatePublished - Mar 13 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Chhabra, A., Lechner, A. J., Ueno, M., Acharya, A., Van Handel, B., Wang, Y., Iruela-Arispe, M. L., Tallquist, M. D., & Mikkola, H. K. A. (2012). Trophoblasts Regulate the Placental Hematopoietic Niche through PDGF-B Signaling. Developmental Cell, 22(3), 651-659. https://doi.org/10.1016/j.devcel.2011.12.022