Faculty Collaboration Database

Temporally resolved early bone morphogenetic protein-driven transcriptional cascade during human amnion specification. Elife 2024 Jul 25;12

Date

07/26/2024

Pubmed ID

39051990

Pubmed Central ID

PMC11272160

DOI

10.7554/eLife.89367

Scopus ID

2-s2.0-85170502786 (requires institutional sign-in at Scopus site)

Abstract

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 bone morphogenetic protein (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 hr 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 K

Authors

Chien-Wei Lin PhD Associate Professor in the Data Science Institute department at Medical College of Wisconsin
Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Kenichiro Taniguchi PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amnion
Animals
Bone Morphogenetic Proteins
Cell Differentiation
Female
Gene Expression Profiling
Gene Expression Regulation, Developmental
Humans
Pluripotent Stem Cells
Pregnancy
Signal Transduction
Transcription Factor AP-2