韩国浦项科技大学Jong Kyoung Kim，奥地利科学院分子生物技术研究所Bon-Kyoung Koo和美国范德比尔特大学医学中心Eunyoung Choi团队共同合作取得重要工作进展。他们研究发现p57^Kip2加强了胃主细胞的储备干细胞状态。该项研究成果2022年5月5日在线发表于《细胞—干细胞》杂志上。

在这里，研究人员将 p57^Kip2 (p57) 鉴定为小鼠主细胞储备干细胞状态的分子开关。在稳态期间，p57在主细胞中不断表达，但在损伤后迅速减少，随后出现强劲增殖。单细胞RNA测序和dox诱导的谱系追踪都证实了p57的连续丢失和主细胞谱系内的增殖激活。在体器官中，p57过表达诱导了长期储备干细胞状态，伴随着生态位需求的改变和成熟的主细胞/分泌表型。在体内p57的组成型表达后，主细胞表现出受损的损伤反应。因此，p57是一个守门人，它使主细胞的储备干细胞状态处于稳态。

据了解，成体干细胞不断对局部变化做出反应，以确保组织内环境稳定。在胃的主体中，主细胞产生消化酶。然而，在损伤后，主细胞会迅速增殖以促进组织再生。

附：英文原文

Title: p57Kip2 imposes the reserve stem cell state of gastric chief cells

Author: Ji-Hyun Lee, Somi Kim, Seungmin Han, Jimin Min, Brianna Caldwell, Aileen-Diane Bamford, Andreia Sofia Batista Rocha, JinYoung Park, Sieun Lee, Szu-Hsien Sam Wu, Heetak Lee, Juergen Fink, Sandra Pilat-Carotta, Jihoon Kim, Manon Josserand, Réka Szep-Bakonyi, Yohan An, Young Seok Ju, Anna Philpott, Benjamin D. Simons, Daniel E. Stange, Eunyoung Choi, Bon-Kyoung Koo, Jong Kyoung Kim

Issue&Volume: 2022/05/05

Abstract: Adult stem cells constantly react to local changes to ensure tissue homeostasis. In the main body of the stomach, chief cells produce digestive enzymes; however, upon injury, they undergo rapid proliferation for prompt tissue regeneration. Here, we identified p57Kip2 (p57) as a molecular switch for the reserve stem cell state of chief cells in mice. During homeostasis, p57 is constantly expressed in chief cells but rapidly diminishes after injury, followed by robust proliferation. Both single-cell RNA sequencing and dox-induced lineage tracing confirmed the sequential loss of p57 and activation of proliferation within the chief cell lineage. In corpus organoids, p57 overexpression induced a long-term reserve stem cell state, accompanied by altered niche requirements and a mature chief cell/secretory phenotype. Following the constitutive expression of p57 in vivo, chief cells showed an impaired injury response. Thus, p57 is a gatekeeper that imposes the reserve stem cell state of chief cells in homeostasis.

DOI: 10.1016/j.stem.2022.04.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00154-0