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Islam, M. R.

Publications and source records attributed to Islam, M. R..

2 recordsLinked to original sources
bioRxiv2019

Atypical Protein Kinase C iota (PKC{lambda}/{iota}) Ensures Mammalian Development by Establishing the Maternal-Fetal Exchange Interface

In utero mammalian development relies on the establishment of the maternal-fetal exchange interface, which ensures transportation of nutrients and gases between the mother and the fetus. This exchange interface is established via development of multinucleated syncytiotrophoblast cells (SynTs) during placentation. In mouse, SynTs develop via differentiation of the trophoblast progenitor cells (TSPCs) of the placenta primordium and in human, SynTs are developed via differentiation of villous cytotrophoblast (CTB) progenitors. Despite the critical need in pregnancy progression, conserved signaling mechanisms that ensure SynT development are poorly understood. Herein, we show that Atypical Protein Kinase C iota (PKC{lambda}/I) plays an essential role in establishing the SynT differentiation program in trophoblast progenitors. Loss of PKC{lambda}/I in the mouse TSPCs abrogates SynT development leading to embryonic death at ~E9.0. We also show that PKC{lambda}/I-mediated priming of trophoblast progenitors for SynT differentiation is a conserved event during human placentation. PKC{lambda}/I is selectively expressed in the first-trimester CTBs of a developing human placenta. Furthermore, loss of PKC{lambda}/I in CTB-derived human trophoblast stem cells (Human TSCs) impairs their SynT differentiation potential both in vitro and after transplantation in immunocompromised mice. Our mechanistic analyses indicate that PKC{lambda}/I signaling maintains expression of GCM1, GATA2, and PPAR{gamma}, which are key transcription factors to instigate SynT differentiation programs in both mouse and human trophoblast progenitors. Our study uncovers a conserved molecular mechanism, in which PKC{lambda}/I signaling regulates establishment of the maternal-fetal exchange surface by promoting trophoblast progenitor to SynT transition during placentation.

developmental biology↗
bioRxiv2019

Trophoblast paracrine signaling regulates placental hematoendothelial niche

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.

developmental biology↗