Division-Independent Differentiation of Muscle Stem Cells During a Growth Stimulus

Author:

Ismaeel Ahmed12ORCID,Goh Jensen12,Brooks Mobley C3,Murach Kevin A24,Brett Jamie O56,de Morrée Antoine57,Rando Thomas A58,Peterson Charlotte A29,Wen Yuan12,McCarthy John J12ORCID

Affiliation:

1. Department of Physiology, University of Kentucky , Lexington, KY , USA

2. Center for Muscle Biology, University of Kentucky , Lexington, KY , USA

3. School of Kinesiology, Auburn University , Auburn, AL , USA

4. Department Health, Human Performance, & Recreation, University of Arkansas , Fayetteville, AR , USA

5. Department of Neurology and Neurological Sciences, Stanford University School of Medicine , Stanford, CA , USA

6. Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA , USA

7. Department of Biomedicine, Aarhus University , Aarhus C , Denmark

8. Broad Stem Cell Research Center, University of California Los Angeles , Los Angeles, CA , USA

9. Department of Physical Therapy, University of Kentucky , Lexington, KY , USA

Abstract

Abstract Adult muscle stem cells (MuSCs) are known to replicate upon activation before differentiating and fusing to regenerate myofibers. It is unclear whether MuSC differentiation is intrinsically linked to cell division, which has implications for stem cell population maintenance. We use single-cell RNA-sequencing to identify transcriptionally diverse subpopulations of MuSCs after 5 days of a growth stimulus in adult muscle. Trajectory inference in combination with a novel mouse model for tracking MuSC-derived myonuclei and in vivo labeling of DNA replication revealed an MuSC population that exhibited division-independent differentiation and fusion. These findings demonstrate that in response to a growth stimulus in the presence of intact myofibers, MuSC division is not obligatory.

Funder

National Institutes of Health

National Institute on Aging

National Institutes of Arthritis and Musculoskeletal and Skin Diseases

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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