Isl1 identifies the extraembryonic mesodermal / allantois progenitors and required for placenta morphogenesis and vasculature formation [RNA-Seq]

The transcription factor Isl1 is expressed in the progenitors of the Ex-Mes and allantois, however its role in the placentation remains unclear. Our studies showed that deletion of Isl1 causes defects in allantois growth, chorioallantoic fusion and placenta vessel morphogenesis. RNA-seq analyses have revealed that Isl1 regulates the expression of genes important for Ex-Mes multipotency, differentiation and diversification. Isl1 promotes allantoic endothelial but inhibits mesenchymal cell differentiation. Isl1 plays an important role in regulating multiple genetic and epigenetic pathways of vascular morphogenesis. Allantoic signals regulated by Isl1 in turn mediate the inductive interactions between the allantois and chorion critical for chorionic epithelium differentiation, villous formation, and labyrinth angiogenesis. In conclusion, our study provides an integrated insight into the mechanisms underlying placental lineage differentiation, diversification, and vascular formation, highlighting the necessity of Isl1 for early placenta morphogenesis. Our study suggests the potential utility of Isl1 in regenerative medicine application using the stem cells derived from the placenta, umbilical cord and amnionic membrane.