부산대학교 도서관

The signalling pathways that maintain primed human pluripotent stem cells (hPSCs) have been well characterised, revealing a critical role for TGF[beta]/Activin/Nodal signalling. In contrast, the signalling requirements of naive human pluripotency have not been fully established. Here, we demonstrate that TGF[beta] signalling is required to maintain naive hPSCs. The downstream effector proteins -- SMAD2/3 -- bind common sites in naive and primed hPSCs, including shared pluripotency genes. In naive hPSCs, SMAD2/3 additionally bind to active regulatory regions near to naive pluripotency genes. Inhibiting TGF[beta] signalling in naive hPSCs causes the downregulation of SMAD2/3-target genes and pluripotency exit. Single-cell analyses reveal that naive and primed hPSCs follow different transcriptional trajectories after inhibition of TGF[beta] signalling. Primed hPSCs differentiate into neuroectoderm cells, whereas naive hPSCs transition into trophectoderm. These results establish that there is a continuum for TGF[beta] pathway function in human pluripotency spanning a developmental window from naive to primed states.
Byline: Anna Osnato, Stephanie Brown, Christel Krueger, Simon Andrews, Amanda J Collier, Shota Nakanoh, Mariana Quiroga Londoño, Brandon T Wesley, Daniele Muraro, A Sophie Brumm, Kathy K Niakan, Ludovic Vallier, [...]