School of Biomedical Sciences cordially invites you to join the following seminar:

Speaker: Professor Michael A Rudnicki, Director, Regenerative Medicine Program and Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute and University of Ottawa, Canada
Talk Title: Developing innovative regenerative therapies for neuromuscular diseases

Date: 14 November 2024 (Thursday)
Time: 4:30 pm – 5:30 pm
Venue: Seminar Room 3, G/F, Laboratory Block, 21 Sassoon Road
Host: Professor Zhongjun Zhou

Biography

Michael Rudnicki is a Senior Scientist and the Director of the Regenerative Medicine Program and the Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute. He is Professor in the Department of Medicine at the University of Ottawa. Dr. Rudnicki is CEO and Scientific Director of the Canadian Stem Cell Network (SCN). Dr. Rudnicki’s achievements have been recognized by numerous honours including being named a Tier 1 Canada Research Chair, an International Research Scholar of the Howard Hughes Medical Institute for two consecutive terms, a Fellow of the Royal Society of Canada, an Officer of the Order of Canada, and a Fellow of the Royal Society (London). He has been a founder in several spin-off biotechnology companies including Satellos Bioscience.

Abstract

Satellite cells and their progenitors are thought to be organized hierarchically with functional heterogeneity existing withing different subsets of quiescent cells. How satellite cells balance the generation progenitors while maintaining self-renewal can be posited as either stochastic fate acquisition, or a hierarchical organization of asymmetric divisions with determined cell fates. Previously, we identified a putative stem cell within the satellite cell population using Cre-LoxP lineage tracing. We found committed satellite myogenic cells express high levels of Myf5-Cre (YFP⁺), whereas 8 % of satellite stem cells have never expressed Myf5-Cre (YFP^-). Engraftment experiments established that satellite stem cells (Pax7⁺/Myf5^low) reconstitute the self-renewing satellite cell population following transplantation whereas satellite myogenic cells cannot efficiently reconstitute this population. Satellite stem cells are multipotential and can generate both muscle and brown fat. Thus, this sub-compartment fulfill the defining criteria of adult stem cells in that they exhibit long-term self-renewal and are multipotential. Therefore, we performed single-cell RNA-seq and gene expression analysis on YFP- (Myf5^low) populations enriched for the satellite stem cell population and defined a novel cluster. We identified unique cell surface markers that facilitate prospective isolation of a distinct subpopulation of Myf5^low cells. Engraftment experiments demonstrate that this subset of MuSCs exhibits superior stem-like characteristics, enhanced self-renewal, and are deeply quiescent. They exhibit low metabolic activity, markedly reduced mitochondrial membrane potential (MMP), and smaller fragmented mitochondria with high levels of pDRP-1. We conclude that Myf5^low MuSCs represent a distinct subpopulation of satellite cells with very low metabolic requirements, which represent long term self-renewing muscle stem cells (LT-MuSCs).

ALL ARE WELCOME.