Zmpste24 is a zinc ion-binding metalloproteinase that is involved in lamin A processing and maturation. Dysfunction of Zmpste24 in human results in accumulation of farnesylated prelamin A, which leads to the Hutchinson–Gilford progeria syndromes (HGPS). However, the impact of HGPS on the function of muscle satellite cells (MuSCs) (i.e., muscle stem cells) is not well characterized. Using a Zmpste24 knockout (KO) mouse model that recapitulates many features of HGPS, we observed an obvious delay in injury-induced muscle regeneration in 5-month-old Zmpste24 KO mice. Interestingly, unlike MuSCs from younger Zmpste24 KO mice, those from 5-month-old Zmpste24 KO mice showed obvious cell cycle re-entry defects both in culture and in vivo, which is certainly responsible for the regenerat...[ Read more ]

Zmpste24 is a zinc ion-binding metalloproteinase that is involved in lamin A processing and maturation. Dysfunction of Zmpste24 in human results in accumulation of farnesylated prelamin A, which leads to the Hutchinson–Gilford progeria syndromes (HGPS). However, the impact of HGPS on the function of muscle satellite cells (MuSCs) (i.e., muscle stem cells) is not well characterized. Using a Zmpste24 knockout (KO) mouse model that recapitulates many features of HGPS, we observed an obvious delay in injury-induced muscle regeneration in 5-month-old Zmpste24 KO mice. Interestingly, unlike MuSCs from younger Zmpste24 KO mice, those from 5-month-old Zmpste24 KO mice showed obvious cell cycle re-entry defects both in culture and in vivo, which is certainly responsible for the regeneration defects. Moreover, we also observed a decrease in the number of quiescent MuSCs in Zmpste24 KO mice, which also contributed to delayed regeneration process. To gain mechanistic insights, we performed RNA-seq to compare the transcriptomes of MuSCs from 5-month-old KO and control mice. More in-depth study is needed to further elucidate the pathogenic mechanisms underlying the activation defects seen in Zmpste24 KO MuSCs.

Keywords: Zmpste24    HGPS    MuSCs    cell cycle re-entey