| First Author | Linneberg-Agerholm M | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 15 | Pages | 4010-4029.e16 |
| PubMed ID | 38917790 | Mgi Jnum | J:351384 |
| Mgi Id | MGI:7703036 | Doi | 10.1016/j.cell.2024.05.051 |
| Citation | Linneberg-Agerholm M, et al. (2024) The primitive endoderm supports lineage plasticity to enable regulative development. Cell |
| abstractText | Mammalian blastocyst formation involves the specification of the trophectoderm followed by the differentiation of the inner cell mass into embryonic epiblast and extra-embryonic primitive endoderm (PrE). During this time, the embryo maintains a window of plasticity and can redirect its cellular fate when challenged experimentally. In this context, we found that the PrE alone was sufficient to regenerate a complete blastocyst and continue post-implantation development. We identify an in vitro population similar to the early PrE in vivo that exhibits the same embryonic and extra-embryonic potency and can form complete stem cell-based embryo models, termed blastoids. Commitment in the PrE is suppressed by JAK/STAT signaling, collaborating with OCT4 and the sustained expression of a subset of pluripotency-related transcription factors that safeguard an enhancer landscape permissive for multi-lineage differentiation. Our observations support the notion that transcription factor persistence underlies plasticity in regulative development and highlight the importance of the PrE in perturbed development. |