Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells.

Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells.

Loeffler, Dirk;Wehling, Arne;Schneiter, Florin;Zhang, Yang;Müller-Bötticher, Niklas;Hoppe, Philipp S;Hilsenbeck, Oliver;Kokkaliaris, Konstantinos D;Endele, Max;Schroeder, Timm;
Nature 2019 Vol. 573 pp. 426-429
229
loeffler2019asymmetricnature

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 shown. 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 division. 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.

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