Asymmetric organelle inheritance predicts human blood stem cell fate
| Autor: | Markus G. Manz, Dirk Loeffler, Arne Wehling, Florin Schneiter, Tobias Kull, Claudia Lengerke, Timm Schroeder, Weijia Wang |
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| Přispěvatelé: | University of Zurich |
| Rok vydání: | 2022 |
| Předmět: |
Cell division
Endosome Immunology 610 Medicine & health Endosomes Biology Stem cell marker Biochemistry Mice Organelle Asymmetric cell division medicine Animals Humans Asymmetric Cell Division Hematopoietic stem cell Cell Differentiation Cell Biology Hematology Hematopoietic Stem Cells Cell biology medicine.anatomical_structure 10032 Clinic for Oncology and Hematology Blood Commentary Stem cell Organelle inheritance Cell Division |
| Zdroj: | Blood, 139 (13) Blood |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.2020009778 |
| Popis: | Understanding human hematopoietic stem cell fate control is important for its improved therapeutic manipulation. Asymmetric cell division, the asymmetric inheritance of factors during division instructing future daughter cell fates, was recently described in mouse blood stem cells. In human blood stem cells, the possible existence of asymmetric cell division remained unclear because of technical challenges in its direct observation. Here, we use long-term quantitative single-cell imaging to show that lysosomes and active mitochondria are asymmetrically inherited in human blood stem cells and that their inheritance is a coordinated, nonrandom process. Furthermore, multiple additional organelles, including autophagosomes, mitophagosomes, autolysosomes, and recycling endosomes, show preferential asymmetric cosegregation with lysosomes. Importantly, asymmetric lysosomal inheritance predicts future asymmetric daughter cell-cycle length, differentiation, and stem cell marker expression, whereas asymmetric inheritance of active mitochondria correlates with daughter metabolic activity. Hence, human hematopoietic stem cell fates are regulated by asymmetric cell division, with both mechanistic evolutionary conservation and differences to the mouse system. |
| Databáze: | OpenAIRE |
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