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

Autor(en)

Amol Ugale, Dhanlakshmi Shunmugam, Lokesh G Pimpale, Elisabeth Rebhan, Manuela Baccarini

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.

Organisation(en)

Department für Mikrobiologie, Immunbiologie und Genetik, Max Perutz Labs

Externe Organisation(en)

HeartBeat.bio

Journal

The Journal of Cell Biology (JCB)

Band

223

ISSN

0021-9525

DOI

https://doi.org/10.1083/jcb.202310137

Publikationsdatum

09-2024

Peer-reviewed

Ja

ÖFOS 2012

106039 Stammzellenforschung, 106023 Molekularbiologie, 106052 Zellbiologie

Schlagwörter

ASJC Scopus Sachgebiete

Cell Biology

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/461898fb-e6d6-480d-88c7-8dc6d12b91c9