伴侶蛋白介導的自噬維持了造血幹細胞的功能

伴侶蛋白介導的自噬維持了造血幹細胞的功能

作者：

小柯機器人

發布時間：2021/1/15 15:40:50

2021年1月13日出版的《自然》雜誌在線發表了美國阿爾伯特·愛因斯坦醫學院Ana Maria Cuervo和Britta Will小組合作的研究成果，他們發現伴侶素介導的自噬維持了造血幹細胞（HSC）的功能。

研究人員發現伴侶素介導的自噬（CMA）參與維持成年小鼠HSC的功能，CMA是一種溶酶體選擇性降解蛋白質的形式。CMA是幹細胞蛋白質質量控制和HSC活化後脂肪酸代謝上調所必需的。研究發現隨著年齡的增長，HSC中CMA的活性降低，並證明利用遺傳手段或藥物激活CMA可以恢復小鼠和人類HSC的功能。

總之，該發現為理解CMA在維持HSC質量控制、適當能量學和HSC長時功能中的作用提供了見解。該工作表明，CMA可能是衰老或幹細胞移植等過程中增強HSC功能的潛在靶點。

據了解，大部分靜息HSC的激活是血細胞終身產生的先決條件。這個過程需要對主要生物分子調控以滿足HSC分裂和代謝需求。但是幹細胞活化後調控細胞重編程以及其隨後恢復靜息的機制尚未得到充分表徵。

附：英文原文

Title: Chaperone-mediated autophagy sustains haematopoietic stem-cell function

Author: Shuxian Dong, Qian Wang, Yun-Ruei Kao, Antonio Diaz, Inmaculada Tasset, Susmita Kaushik, Victor Thiruthuvanathan, Aliona Zintiridou, Edward Nieves, Monika Dzieciatkowska, Julie A. Reisz, Evripidis Gavathiotis, Angelo DAlessandro, Britta Will, Ana Maria Cuervo

Issue&Volume: 2021-01-13

Abstract: The activation of mostly quiescent haematopoietic stem cells (HSCs) is a prerequisite for life-long production of blood cells1. This process requires major molecular adaptations to allow HSCs to meet the regulatory and metabolic requirements for cell division2,3,4. The mechanisms that govern cellular reprograming upon stem-cell activation, and the subsequent return of stem cells to quiescence, have not been fully characterized. Here we show that chaperone-mediated autophagy (CMA)5, a selective form of lysosomal protein degradation, is involved in sustaining HSC function in adult mice. CMA is required for protein quality control in stem cells and for the upregulation of fatty acid metabolism upon HSC activation. We find that CMA activity in HSCs decreases with age and show that genetic or pharmacological activation of CMA can restore the functionality of old mouse and human HSCs. Together, our findings provide mechanistic insights into a role for CMA in sustaining quality control, appropriate energetics and overall long-term HSC function. Our work suggests that CMA may be a promising therapeutic target for enhancing HSC function in conditions such as ageing or stem-cell transplantation.

DOI: 10.1038/s41586-020-03129-z

Source: https://www.nature.com/articles/s41586-020-03129-z