posted on 2025-01-24, 10:13authored byA 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 S Hill, Kathy K Niakan
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.
Funding
Crick (Grant ID: CC2021, Grant title: Hill CC2021)
Crick (Grant ID: CC2074, Grant title: Niakan CC2074)
Crick (Grant ID: CC1069, Grant title: STP Light Microscopy)