美国纪念斯隆·凯特琳癌症中心的Lorenz Studer研究组的最新发现，在人类多潜能干细胞中，脂质缺乏诱导产生一种稳定的、由初始到激活的多能性中间态。这一研究成果发表在2019年7月3日出版的国际学术期刊《细胞—干细胞l》上。

研究人员发现，广泛使用的E8培养基能够将hPSC维持在多潜能性初始到活化的中间状态；尽管细胞培养在活化态维持条件中，细胞仍具有初始态类似的发育特征以及生物能量和表观基因组的特征。转录水平上，E8培养的hPSC具有激活的脂质合成以及抑制的MAPK/TGF-β基因表达，因此内源性ERK被抑制。这些特征依赖于无脂质的培养条件，一旦接触脂质便丢失，而短期药物抑制ERK能够在脂质存在的情况下维持初始到活化的中间态。最后，研究人员发现，脂质从头合成是E8培养的hPSC以及人上胚层体内着床前的共有转录特征。这些发现表明，外源性脂质的存在参与调控人干细胞的多潜能性，并确立E8培养的hPSC处在一个稳定的初始到活化多潜能中间态。

据介绍，当前研究对获取初始状态的人类多潜能干细胞（hPSC）中所遇到的挑战表明，参与调控多潜能性的初始态与活化态的因子还未完全定义。

附：英文原文

Title: Lipid Deprivation Induces a Stable, Naive-to-Primed Intermediate State of Pluripotency in Human PSCs

Author: Daniela Cornacchia, Chao Zhang, Bastian Zimmer, Justin R. Cross, Doron Betel, Lorenz Studer

Issue&Volume: Jul 03, 2019 Volume 25Issue 1

Abstract: Current challenges in capturing naive human pluripotent stem cells (hPSCs) suggest that the factors regulating human naive versus primed pluripotency remain incompletely defined. Here we demonstrate that the widely used Essential 8 minimal medium (E8) captures hPSCs at a naive-to-primed intermediate state of pluripotency expressing several naive-like developmental, bioenergetic, and epigenomic features despite providing primed-state-sustaining growth factor conditions. Transcriptionally, E8 hPSCs are marked by activated lipid biosynthesis and suppressed MAPK/TGF-β gene expression, resulting in endogenous ERK inhibition. These features are dependent on lipid-free culture conditions and are lost upon lipid exposure, whereas short-term pharmacological ERK inhibition restores naive-to-primed intermediate traits even in the presence of lipids. Finally, we identify de novo lipogenesis as a common transcriptional signature of E8 hPSCs and the pre-implantation human epiblast in vivo. These findings implicate exogenous lipid availability in regulating human pluripotency and define E8 hPSCs as a stable, naive-to-primed intermediate ( NPI) pluripotent state.

DOI: https://doi.org/10.1016/j.stem.2019.05.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30205-X