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Nature. 2019 Sep;573(7774):426-429. doi: 10.1038/s41586-019-1531-6. Epub 2019 Sep 4.

Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells.

Author information

1
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
2
Research Unit Stem Cell Dynamics, Helmholtz Center Munich - German Research Center for Environmental Health, Neuherberg, Germany.
3
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. timm.schroeder@bsse.ethz.ch.
4
Research Unit Stem Cell Dynamics, Helmholtz Center Munich - German Research Center for Environmental Health, Neuherberg, Germany. timm.schroeder@bsse.ethz.ch.

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 machinery-including lysosomes, autophagosomes, mitophagosomes and the protein NUMB-can 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.

PMID:
31485073
DOI:
10.1038/s41586-019-1531-6

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