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

A. Ismaeel, J. Goh, C. B. Mobley, K. A. Murach, J. O. Brett, A. de Morree, T. A. Rando, C. A. Peterson, Y. Wen, J. J. McCarthy

Research output: Contribution to journalArticlepeer-review

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.
Original languageAmerican English
Pages (from-to)266-277
Number of pages12
JournalStem Cells
Volume42
Issue number3
DOIs
StatePublished - 2024

Bibliographical note

Ismaeel, Ahmed Goh, Jensen Mobley, C Brooks Murach, Kevin A Brett, Jamie O de Morree, Antoine Rando, Thomas A Peterson, Charlotte A Wen, Yuan McCarthy, John J eng K99 AR081367/AR/NIAMS NIH HHS/ R00 AR081367/AR/NIAMS NIH HHS/ AG069909/AG/NIA NIH HHS/ R01 AR073248/AR/NIAMS NIH HHS/ R01 AG069909/AG/NIA NIH HHS/ NH/NIH HHS/ R01 AG068667/AG/NIA NIH HHS/ P01 AG036695/AG/NIA NIH HHS/ K99 AG063994/AG/NIA NIH HHS/ England 2023/12/09 Stem Cells. 2024 Mar 14;42(3):266-277. doi: 10.1093/stmcls/sxad091.

Keywords

  • Animals Mice *Muscle, Skeletal Cell Differentiation *Adult Stem Cells Cell Division DNA replication adult stem cells single-cell gene expression analysis

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