![]() ![]() ![]() The Author(s) under exclusive licence to Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences.Darwin Prockop, M.D., Ph.D., director of the Texas A&M Health Science Center Institute for Regenerative Medicine at Scott & White, answers your questions about this complex and rapidly developing field. Together, our findings connect the embryonic factor Lin28a to adult stem cell self-renewal and juvenile regeneration. Functionally, conditional ablation and induction of Lin28a + MuSCs in adult mice revealed that these cells are necessary and sufficient for efficient muscle regeneration. In addition, RNA-sequencing revealed that Lin28a + MuSCs co-expressed higher levels of certain embryonic limb bud transcription factors, telomerase components and the p53 inhibitor Mdm4, and lower levels of myogenic differentiation markers compared to adult Pax7 + MuSCs, resulting in enhanced self-renewal and stress-response signatures. The epigenome of adult Lin28a + MuSCs showed resemblance to embryonic muscle progenitors. Compared with adult Pax7 + MuSCs, Lin28a + MuSCs displayed enhanced myogenic potency in vitro and in vivo upon transplantation. Here, we show that Lin28a is expressed in embryonic limb bud muscle progenitors, and that a rare reserve subset of Lin28a +Pax7 - skeletal MuSCs can respond to injury at adult stage by replenishing the Pax7 + MuSC pool to drive muscle regeneration. However, much remains unclear regarding the heterogeneous capacity of MuSCs for self-renewal and regeneration. homeostasis and after injury, adult muscle stem cells (MuSCs) activate to mediate muscle regeneration. 12 University of Chinese Academy of Sciences, Beijing, China. 11 Beijing Institute for Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. 10 Institute of Zoology, Chinese Academy of Sciences, Beijing, China.1 Institute of Zoology, Chinese Academy of Sciences, Beijing, China. ![]() 9 Department of Clinical Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.8 CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.7 Laboratory of Cancer Epigenome, Division of Medical Science, National Cancer Centre Singapore, Singapore, Singapore.6 Laboratory of Cancer Therapeutics, Program in Cancer and Stem Cell Biology, Duke-National University of Singapore Medical School, Singapore, Singapore.5 Institute of Molecular and Cell Biology, Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.4 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore.3 University of Chinese Academy of Sciences, Beijing, China.2 Beijing Institute for Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.1 Institute of Zoology, Chinese Academy of Sciences, Beijing, China. ![]()
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