小柯机器人

2021年1月13日出版的《自然》杂志在线发表了美国阿尔伯特·爱因斯坦医学院Ana Maria Cuervo和Britta Will小组合作的研究成果，他们发现伴侣素介导的自噬维持了造血干细胞（HSC）的功能。

研究人员发现伴侣素介导的自噬（CMA）参与维持成年小鼠HSC的功能，CMA是一种溶酶体选择性降解蛋白质的形式。CMA是干细胞蛋白质质量控制和HSC活化后脂肪酸代谢上调所必需的。研究发现随着年龄的增长，HSC中CMA的活性降低，并证明利用遗传手段或药物激活CMA可以恢复小鼠和人类HSC的功能。

总之，该发现为理解CMA在维持HSC质量控制、适当能量学和HSC长时功能中的作用提供了见解。该工作表明，CMA可能是衰老或干细胞移植等过程中增强HSC功能的潜在靶点。

据了解，大部分静息HSC的激活是血细胞终身产生的先决条件。这个过程需要对主要生物分子调控以满足HSC分裂和代谢需求。但是干细胞活化后调控细胞重编程以及其随后恢复静息的机制尚未得到充分表征。

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

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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