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Trophoblasts regulate the placental hematopoietic niche through PDGF-B signaling.


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, PDGFR?, 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.

SUBMITTER: Chhabra A 

PROVIDER: S-EPMC3395466 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Trophoblasts regulate the placental hematopoietic niche through PDGF-B signaling.

Chhabra Akanksha A   Lechner Andrew J AJ   Ueno Masaya M   Acharya Asha A   Van Handel Ben B   Wang Yanling Y   Iruela-Arispe M Luisa ML   Tallquist Michelle D MD   Mikkola Hanna K A HK  

Developmental cell 20120301 3


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 proli  ...[more]

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