RT Journal Article SR Electronic T1 Single-cell RNA-seq reveals heterogeneity in hiPSC-derived muscle progenitors and E2F family as a key regulator of proliferation JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202101312 DO 10.26508/lsa.202101312 VO 5 IS 8 A1 Minas Nalbandian A1 Mingming Zhao A1 Hiroki Kato A1 Tatsuya Jonouchi A1 May Nakajima-Koyama A1 Takuya Yamamoto A1 Hidetoshi Sakurai YR 2022 UL https://www.life-science-alliance.org/content/5/8/e202101312.abstract AB Human pluripotent stem cell-derived muscle progenitor cells (hiPSC-MuPCs) resemble fetal-stage muscle progenitor cells and possess in vivo regeneration capacity. However, the heterogeneity of hiPSC-MuPCs is unknown, which could impact the regenerative potential of these cells. Here, we established an hiPSC-MuPC atlas by performing single-cell RNA sequencing of hiPSC-MuPC cultures. Bioinformatic analysis revealed four cell clusters for hiPSC-MuPCs: myocytes, committed, cycling, and noncycling progenitors. Using FGFR4 as a marker for noncycling progenitors and cycling cells and CD36 as a marker for committed and myocyte cells, we found that FGFR4+ cells possess a higher regenerative capacity than CD36+ cells. We also identified the family of E2F transcription factors are key regulators of hiPSC-MuPC proliferation. Our study provides insights on the purification of hiPSC-MuPCs with higher regenerative potential and increases the understanding of the transcriptional regulation of hiPSC-MuPCs.