小柯机器人

溶酶体分配影响造血干细胞命运
2019-09-05 15:59

瑞士苏黎世联邦理工学院Timm Schroeder研究小组近日取得一项新成果。他们发现不对称溶酶体分配能够预测造血干细胞的活化。相关论文2019年9月4日在线发表在《自然》上。

研究人员证明细胞降解机器,包括溶酶体、自噬体、线粒体和NUMB蛋白,可以不对称地分配到造血干细胞子细胞中。这种不对称分配预测了将来不对称的代谢和翻译活化以及造血干细胞子细胞及其后代的命运。因此,这项研究为造血干细胞中不对称细胞分裂的存在提供了证据。

研究人员表示,造血干细胞在整个生命过程中自我更新并分化成所有血液谱系,并且可以在移植后修复受损的血液系统。先前的研究已经怀疑不对称细胞分裂是造血干细胞命运的调节因子,但其存在并未被直接揭示。在不对称细胞分裂中,未来子细胞的不对称命运通过与有丝分裂相关的机制提前确定。这可以通过细胞与外界微环境信号的不对称遗传来介导,例如通过分裂平面的方向或通过细胞内在命运决定因素的不对称遗传。不对称遗传或不对称子细胞命运的观察结果不足以证明不对称细胞分裂。在这两种情况下,姐妹细胞命运可以通过独立于分裂的机制来控制。

附:英文原文

Title: Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells

Author: Dirk Loeffler, Arne Wehling, Florin Schneiter, Yang Zhang, Niklas Mller-Btticher, Philipp S. Hoppe, Oliver Hilsenbeck, Konstantinos D. Kokkaliaris, Max Endele, Timm Schroeder

Issue&Volume: 2019-09-04

Abstract: Haematopoietic stem cells self-renew and differentiate into all blood lineages throughout life, and can repair damaged blood systems upon transplantation. Asymmetric cell division has previously been suspected to be a regulator of haematopoietic-stem-cell fate, but its existence has not directly been shown1. In asymmetric cell division, asymmetric fates of future daughter cells are prospectively determined by a mechanism that is linked to mitosis. This can be mediated by asymmetric inheritance of cell-extrinsic niche signals by, for example, orienting the divisional plane, or by the asymmetric inheritance of cell-intrinsic fate determinants. Observations of asymmetric inheritance or of asymmetric daughter-cell fates alone are not sufficient to demonstrate asymmetric cell division2. In both cases, sister-cell fates could be controlled by mechanisms that are independent of division. Here we demonstrate that the cellular degradative machineryincluding lysosomes, autophagosomes, mitophagosomes and the protein NUMBcan be asymmetrically inherited into haematopoietic-stem-cell daughter cells. This asymmetric inheritance predicts the asymmetric future metabolic and translational activation and fates of haematopoietic-stem-cell daughter cells and their offspring. Therefore, our studies provide evidence for the existence of asymmetric cell division in haematopoietic stem cells.

DOI: 10.1038/s41586-019-1531-6

Source:https://www.nature.com/articles/s41586-019-1531-6

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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