Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/192505
Title: | Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice |
Author: | Montserrat Vazquez, Sara Ali, Noelle J. Matteini, Francesca Lozano, Javier Zhaowei, Tu Mejia Ramirez, Eva Marka, Gina Vollmer, Angelika Soller, Karin Sacma, Mehmet Sakk, Vadim Mularoni, Loris Mallm, Jan Philipp Plass, Mireya Zheng, Yi Geiger, Hartmut Florian, M. Carolina |
Keywords: | Medicina regenerativa Cèl·lules mare Regenerative medicine Stem cells |
Issue Date: | 29-Dec-2022 |
Publisher: | Springer Science and Business Media LLC |
Abstract: | One goal of regenerative medicine is to rejuvenate tissues and extend lifespan by restoring the function of endogenous aged stem cells. However, evidence that somatic stem cells can be targeted in vivo to extend lifespan is still lacking. Here, we demonstrate that after a short systemic treatment with a specific inhibitor of the small RhoGTPase Cdc42 (CASIN), transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mice without additional treatment. In detail, we show that systemic CASIN treatment improves strength and endurance of aged mice by increasing the myogenic regenerative potential of aged skeletal muscle stem cells. Further, we show that CASIN modifies niche localization and H4K16ac polarity of HSCs in vivo. Single-cell profiling reveals changes in HSC transcriptome, which underlie enhanced lymphoid and regenerative capacity in serial transplantation assays. Overall, we provide proof-of-concept evidence that a short systemic treatment to decrease Cdc42 activity improves the regenerative capacity of different endogenous aged stem cells in vivo, and that rejuvenated HSCs exert a broad systemic effect sufficient to extend murine health- and lifespan. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41536-022-00275-y |
It is part of: | npj Regenerative Medicine, 2022, vol. 7, num. 78 |
URI: | http://hdl.handle.net/2445/192505 |
Related resource: | https://doi.org/10.1038/s41536-022-00275-y |
ISSN: | 2057-3995 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
s41536-022-00275-y (1).pdf | 4.31 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License