原始内胚层支持谱系可塑性来实现调节性发育
丹麦哥本哈根大学Joshua M. Brickman研究组发现，原始内胚层支持谱系可塑性来实现调节性发育。2024年6月24日，国际知名学术期刊《细胞》在线发表了这一成果。
研究人员表示，哺乳动物囊胚的形成过程包括滋养层外胚层的分化，以及内细胞团向胚胎外胚层和胚胎外原始内胚层（PrE）的分化。在此期间，胚胎保持着可塑性窗口，当受到实验挑战时，可重新定向其细胞命运。
在这种情况下，研究人员发现仅PrE就足以再生出完整的囊胚并继续植入后的发育。研究人员发现了一种与体内早期PrE相似的体外群体，它具有相同的胚胎和胚外潜力，并能形成基于干细胞的完整胚胎模型，称为类囊胚。JAK/STAT信号抑制了PrE中的确立，并与OCT4和多能相关转录因子亚群的持续表达合作，保护了允许多谱系分化的增强子景观。
这些观察结果支持了转录因子的持续性是调节性发育中可塑性的基础这一观点，并强调了PrE在紊乱发育中的重要性。
附：英文原文
Title: The primitive endoderm supports lineage plasticity to enable regulative development
Author: Madeleine Linneberg-Agerholm, Annika Charlotte Sell, Alba Redó-Riveiro, Marta Perera, Martin Proks, Teresa E. Knudsen, Antonio Barral, Miguel Manzanares, Joshua M. Brickman
Issue&Volume: 2024-06-24
Abstract: Mammalian blastocyst formation involves the specification of the trophectoderm followedby the differentiation of the inner cell mass into embryonic epiblast and extra-embryonicprimitive endoderm (PrE). During this time, the embryo maintains a window of plasticityand can redirect its cellular fate when challenged experimentally. In this context,we found that the PrE alone was sufficient to regenerate a complete blastocyst andcontinue 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 completestem cell-based embryo models, termed blastoids. Commitment in the PrE is suppressedby JAK/STAT signaling, collaborating with OCT4 and the sustained expression of a subsetof pluripotency-related transcription factors that safeguard an enhancer landscapepermissive for multi-lineage differentiation. Our observations support the notionthat transcription factor persistence underlies plasticity in regulative developmentand highlight the importance of the PrE in perturbed development.
DOI: 10.1016/j.cell.2024.05.051
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00595-6
来源：科学网 小柯机器人
