Initiation and maintenance of the pluripotent epiblast in pre-implantation human development is independent of NODAL signaling
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Sophie Brumm Afshan Mccarthy Claudia Gerri Todd Fallesen Laura Woods Riley McMahon Athanasios Papathanasiou Kay Elder Phil Snell Leila Christie Patricia Garcia Valerie Shaikly Mohamed Taranissi Paul Serhal Rabi A Odia Mina Vasilic Anna Osnato Peter J Rugg-Gunn Ludovic Vallier Caroline Hill Kathy NiakanAbstract
The human blastocyst contains the pluripotent epiblast from which human embryonic stem cells (hESCs) can be derived. ACTIVIN/NODAL signaling maintains expression of the transcription factor NANOG and in vitro propagation of hESCs. It is unknown whether this reflects a functional requirement for epiblast development in human embryos. Here, we characterized NODAL signaling activity during pre-implantation human development. We showed that NANOG is an early molecular marker restricted to the nascent human pluripotent epiblast and was initiated prior to the onset of NODAL signaling. We further demonstrated that expression of pluripotency-associated transcription factors NANOG, SOX2, OCT4, and KLF17 were maintained in the epiblast in the absence of NODAL signaling activity. Genome-wide transcriptional analysis showed that NODAL signaling inhibition did not decrease NANOG transcription or impact the wider pluripotency-associated gene regulatory network. These data suggest differences in the signaling requirements regulating pluripotency in the pre-implantation human epiblast compared with existing hESC culture.
Journal details
Journal
Developmental Cell
Volume
60
Issue number
2
Pages
174-185 .e5
Available online
Publication date
Full text links
Publisher website (DOI)
10.1016/j.devcel.2024.10.020
Europe PubMed Central
39561779
Pubmed
39561779
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