Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells

• Published in: Nature (London) Vol. 573; no. 7774; pp. 426 - 429
• Main Authors: Loeffler, Dirk, Wehling, Arne, Schneiter, Florin, Zhang, Yang, Müller-Bötticher, Niklas, Hoppe, Philipp S., Hilsenbeck, Oliver, Kokkaliaris, Konstantinos D., Endele, Max, Schroeder, Timm
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2019; Nature Publishing Group
• Subjects: 13/100; 13/106; 13/21; 13/31; 14; 14/1; 14/19; 14/34; 14/56; 14/63; 42; 42/35; 42/44; 631/532/1542; 631/80/39/2348; 631/80/641/1655; 631/80/642/1624; 631/80/85; 82; Analysis; Asymmetry; Autophagy; Blood; Cell activation; Cell differentiation; Cell division; Cell fate; Hematopoietic stem cells; Heredity; Humanities and Social Sciences; Letter; Lysosomes; Metabolic rate; Mitosis; multidisciplinary; NUMB protein; Offspring; Phagosomes; Proteins; Science; Science (multidisciplinary); Stem cell research; Stem cells; Transplantation; Switzerland
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-019-1531-6

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 1 . 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 2 . 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. The cellular degradative machinery can be asymmetrically inherited upon haematopoietic-stem-cell division, which predicts the future metabolic and translational activation of their daughter cells.