PT  - JOURNAL ARTICLE
AU  - Hu Li
AU  - Qian Chen
AU  - Changyin Li
AU  - Ran Zhong
AU  - Yixia Zhao
AU  - Dahai Zhu
AU  - Yong Zhang
TI  - Loss of muscle stem cells in aged mice is replenished by muscle-secreted niche factor G-CSF
AID  - 10.1101/488874
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 488874
4099  - http://biorxiv.org/content/early/2018/12/06/488874.short
4100  - http://biorxiv.org/content/early/2018/12/06/488874.full
AB  - Summary Function and number of muscle stem cells (satellite cells, SCs) declines with muscle aging. Although SCs are heterogeneous and different subpopulations have been identified, it remains unknown if a specific subpopulation of muscle SCs selectively decreases during aging and whether muscle metabolism plays a niche role in regulating the selected decline. Here, using single cell RNA sequencing, we show Pax7Hi and Pax7Lo cells represent two distinct subpopulations. We further find Pax7Hi cells are not only enriched in glycolytic fibers but reduced in aged muscle. Further, we identify granulocyte-colony stimulating factor (G-CSF) as a muscle-secreted niche factor required for regulating the dynamic heterogeneity of Pax7 SCs in mice by promoting their asymmetric division. Intriguingly, we found an unappreciated role for MyoD in regulating transcription of G-CSF (Csf3) gene in a metabolism-dependent manner in muscle. Together, our findings uncover a metabolic niche role of muscle metabolism in regulating Pax7 SC heterogeneity in mice.HighlightsSingle cell RNA-seq unveils Pax7Hi and Pax7Lo cells are two distinct subpopulationsPax7Hi SCs are enriched in glycolytic fibers and reduced in aging muscleMetabolic niche factor G-CSF is required for regulating dynamic change of Pax7 SCsG-CSF replenishes Pax7Hi cells by stimulating asymmetric division of Pax7Mi cells