title: 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, 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.
authors.affiliation: Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Chhabra
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lechner
authors.forename: Masaya
authors.initials: M
authors.lastname: Ueno
authors.forename: Asha
authors.initials: A
authors.lastname: Acharya
authors.forename: Ben
authors.initials: B
authors.lastname: Van Handel
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wang
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Iruela-Arispe
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tallquist
authors.forename: Hanna K A
authors.initials: HK
authors.lastname: Mikkola
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology; D004921:Erythropoietin / Q000502:physiology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D051379:Mice; D010920:Placenta / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000502:physiology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D004921:Erythropoietin; D020797:Receptor, Platelet-Derived Growth Factor beta