| First Author | Loeffler D | Year | 2019 |
| Journal | Nature | Volume | 573 |
| Issue | 7774 | Pages | 426-429 |
| PubMed ID | 31485073 | Mgi Jnum | J:284706 |
| Mgi Id | MGI:6386018 | Doi | 10.1038/s41586-019-1531-6 |
| Citation | Loeffler D, et al. (2019) Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells. Nature 573(7774):426-429 |
| abstractText | 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. |
