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Hic1 Defines Quiescent Mesenchymal Progenitor Subpopulations with Distinct Functions and Fates in Skeletal Muscle Regeneration

By December 16, 2019No Comments

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This week we profile a recent publication in Cell Stem Cell from the laboratories of Drs. Michael Underhill
(pictured, second from left) and Fabio Rossi (left) at the Biomedical Research Centre at UBC.

Can you provide a brief overview of your lab’s current research focus?

Our laboratories study a population of stem/progenitor cells termed mesenchymal progenitors (MPs). They can be found to varying extents throughout adult tissues, and they play a universal role in tissue renewal and regeneration. We are studying how we can modify their behaviour to enhance their regenerative activity and reduce their reparative/fibrotic activity. In complementary studies, we are also investigating the role of these cells in cancer and they appear to be the cell of origin for certain types of cancers, whereas they make a marked contribution to the tumour microenvironment in other types of cancers. The overarching goal of our research programs is to better understand MP biology in health and disease.

What is the significance of the findings in this publication?

This publication describes the generation of a new set of genetic tools that enable us to better study the activity of MPs. The focus of the paper was examining MPs in skeletal muscle regeneration and we show that they play several critical roles important for muscle regeneration. Interestingly, we also reported that MPs directly contribute to regeneration of various connective tissue structures including the myotendinous junction. The myotendinous junction links muscle to tendon and is essential for transmitting muscle forces to the skeleton. How the myotendinous junction is regenerated following injury is poorly understood and in this paper, we identify a subpopulation of MPs that directly regenerates this structure. Collectively, the results in the paper define a number of important activities of MPs in skeletal muscle regeneration.

What are the next steps for this research?

There are a number of next steps, but collectively our groups are very interested in exploring MP function across a number of models with the ultimate goals of better understanding MP biology in development, growth, health and disease. We are also very interested in exploring the role of MP dysfunction in aging and cancer.

This work was funded by:

This research was supported by multiple funding agencies, including the Canadian Institutes of Health, National Institutes of Health and the Terry Fox Research Institute. We would also like to thank STEMCELL Technologies for providing us with in-development media formulations.

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