Signaling proteins in HSC fate determination are unequally segregated during asymmetric cell division.

Autor:	Ugale A; Department of Microbiology, Max Perutz Labs Vienna, University of Vienna, Immunobiology and Genetics, Vienna, Austria., Shunmugam D; Department of Microbiology, Max Perutz Labs Vienna, University of Vienna, Immunobiology and Genetics, Vienna, Austria.; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna , Vienna, Austria., Pimpale LG; HeartBeat.bio AG , Vienna, Austria., Rebhan E; Department of Microbiology, Max Perutz Labs Vienna, University of Vienna, Immunobiology and Genetics, Vienna, Austria., Baccarini M; Department of Microbiology, Max Perutz Labs Vienna, University of Vienna, Immunobiology and Genetics, Vienna, Austria.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2024 Sep 02; Vol. 223 (9). Date of Electronic Publication: 2024 Jun 14.
DOI:	10.1083/jcb.202310137
Abstrakt:	Hematopoietic stem cells (HSCs) continuously replenish mature blood cells with limited lifespans. To maintain the HSC compartment while ensuring output of differentiated cells, HSCs undergo asymmetric cell division (ACD), generating two daughter cells with different fates: one will proliferate and give rise to the differentiated cells' progeny, and one will return to quiescence to maintain the HSC compartment. A balance between MEK/ERK and mTORC1 pathways is needed to ensure HSC homeostasis. Here, we show that activation of these pathways is spatially segregated in premitotic HSCs and unequally inherited during ACD. A combination of genetic and chemical perturbations shows that an ERK-dependent mechanism determines the balance between pathways affecting polarity, proliferation, and metabolism, and thus determines the frequency of asymmetrically dividing HSCs. Our data identify druggable targets that modulate HSC fate determination at the level of asymmetric division. (© 2024 Ugale et al.)
Databáze:	MEDLINE
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