RT Journal Article
SR Electronic
T1 Trophoblast paracrine signaling regulates placental hematoendothelial niche
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 840660
DO 10.1101/840660
A1 Pratik Home
A1 Ananya Ghosh
A1 Ram Parikshan Kumar
A1 Avishek Ganguly
A1 Bhaswati Bhattacharya
A1 Md. Rashedul Islam
A1 Soma Ray
A1 Sumedha Gunewardena
A1 Soumen Paul
YR 2019
UL http://biorxiv.org/content/early/2019/11/14/840660.abstract
AB The placenta acts as a major organ for hematopoiesis. It is believed that placental hematopoietic stem and progenitor cells (HSPCs) migrate to the fetal liver to ensure optimum hematopoiesis in the developing embryo. The labyrinth vasculature in a mid-gestation mouse placenta provides a niche for the definitive hematopoietic stem cell (HSC) generation and expansion. It has been proposed that these processes are regulated by a host of paracrine factors secreted by trophoblast giant cells (TGCs) at the maternal-fetal interface. However, the molecular mechanism by which the TGCs regulate the hematoendothelial niche in a developing placenta is yet to be defined. Using a TGC-specific Gata2 and Gata3 double knockout mouse model, we show that the loss of GATA2 and GATA3 at the TGC layer leads to fetal growth retardation and embryonic death due to disruptions in the delicate hematopoietic-angiogenic balance in the developing placenta. Using single-cell RNA-Seq analyses, we also show that the loss of GATA factors in the TGCs results in the loss of HSC population within the placental labyrinth and is associated with defective placental angiogenesis. Interestingly, we also found that this TGC-specific GATA factor-loss leads to impaired differentiation and distribution of trophoblast progenitor cells. Our study helps to define the GATA-dependent non-autonomous signaling mechanisms of the primary parietal trophoblast giant cells by which it regulates the delicate hematopoietic-angiogenic balance in the developing placenta.