小柯机器人

美国加州大学Robert A.J. Signer研究团队发现Hsf1 促进造血干细胞适应度和蛋白质稳态，以应对体外培养应激和衰老。该项研究成果发表在2021年8月12日出版的《细胞—干细胞》上。

他们确定离体培养的小鼠和人类造血干细胞 (HSC) 迅速增加蛋白质合成。这种对 HSC 蛋白稳态的挑战与 Hsf1 的核积累有关，而 Hsf1 的缺失会损害离体 HSC 的维持。引人注目的是，用小分子补充培养物可增强 Hsf1 激活，部分抑制蛋白质合成，重新平衡蛋白质稳态并支持保留 HSC 系列重组活性。尽管 Hsf1 对体内年轻成年 HSC 是可有可无的，但 Hsf1 缺乏会增加蛋白质合成并损害中年个体 HSC 的重建活性。因此，Hsf1 促进蛋白质稳态和 HSC 的再生活动，以响应培养压力和衰老。

据悉，维持蛋白质稳态是抵抗压力和促进健康衰老的关键。蛋白质稳态对于保持干细胞功能是必要的，但关于在干细胞应激期间调节蛋白质稳态的机制知之甚少，并且在很大程度上尚未探索蛋白质稳态的破坏是否有助于干细胞衰老。

附：英文原文

Title: Hsf1 promotes hematopoietic stem cell fitness and proteostasis in response to ex vivo culture stress and aging

Author: Miriama Kruta, Mary Jean Sunshine, Bernadette A. Chua, Yunpeng Fu, Ashu Chawla, Christopher H. Dillingham, Lorena Hidalgo San Jose, Bijou De Jong, Fanny J. Zhou, Robert A.J. Signer

Issue&Volume: 2021-08-12

Abstract: Maintaining proteostasis is key to resisting stress and promoting healthy aging. Proteostasis is necessary to preserve stem cell function, but little is known about the mechanisms that regulate proteostasis during stress in stem cells, and whether disruptions of proteostasis contribute to stem cell aging is largely unexplored. We determined that ex-vivo-cultured mouse and human hematopoietic stem cells (HSCs) rapidly increase protein synthesis. This challenge to HSC proteostasis was associated with nuclear accumulation of Hsf1, and deletion of Hsf1 impaired HSC maintenance ex vivo. Strikingly, supplementing cultures with small molecules that enhance Hsf1 activation partially suppressed protein synthesis, rebalanced proteostasis, and supported retention of HSC serial reconstituting activity. Although Hsf1 was dispensable for young adult HSCs in vivo, Hsf1 deficiency increased protein synthesis and impaired the reconstituting activity of middle-aged HSCs. Hsf1 thus promotes proteostasis and the regenerative activity of HSCs in response to culture stress and aging.

DOI: 10.1016/j.stem.2021.07.009

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00294-0

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
官方网址：https://www.cell.com/cell-stem-cell/home
投稿链接：https://www.editorialmanager.com/cell-stem-cell/default.aspx