Temporally resolved early BMP-driven transcriptional cascade during human amnion specification. bioRxiv 2024 Mar 06
Date
03/18/2024Pubmed ID
38496419Pubmed Central ID
PMC10942271DOI
10.1101/2023.06.19.545574Abstract
Amniogenesis, a process critical for continuation of healthy pregnancy, is triggered in a collection of pluripotent epiblast cells as the human embryo implants. Previous studies have established that BMP signaling is a major driver of this lineage specifying process, but the downstream BMP-dependent transcriptional networks that lead to successful amniogenesis remain to be identified. This is, in part, due to the current lack of a robust and reproducible model system that enables mechanistic investigations exclusively into amniogenesis. Here, we developed an improved model of early amnion specification, using a human pluripotent stem cell-based platform in which the activation of BMP signaling is controlled and synchronous. Uniform amniogenesis is seen within 48 hours after BMP activation, and the resulting cells share transcriptomic characteristics with amnion cells of a gastrulating human embryo. Using detailed time-course transcriptomic analyses, we established a previously uncharacterized BMP-dependent amniotic transcriptional cascade, and identified markers that represent five distinct stages of amnion fate specification; the expression of selected markers was validated in early post-implantation macaque embryos. Moreover, a cohort of factors that could potentially control specific stages of amniogenesis was identified, including the transcription factor TFAP2A. Functionally, we determined that, once amniogenesis is triggered by the BMP pathway, TFAP2A controls the progression of amniogenesis. This work presents a temporally resolved transcriptomic resource for several previously uncharacterized amniogenesis states and demonstrates a critical intermediate role for TFAP2A during amnion fate specification.
Author List
Sekulovski N, Wettstein JC, Carleton AE, Juga LN, Taniguchi LE, Ma X, Rao S, Schmidt JK, Golos TG, Lin CW, Taniguchi KAuthors
Chien-Wei Lin PhD Associate Professor in the Institute for Health and Equity department at Medical College of WisconsinSridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
