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Cell reprogramming has revolutionized cell and regenerative biology field. However, human iPS derivation remains inefficient and variable. A better knowledge of molecular processes and the rationale underlying the importance of somatic cell origin is crucial to uncover reprogramming mechanisms. Here, we analyze the molecular profile of different human somatic cell types. We show menstrual blood-derived stromal cells (MnSCs) have a distinct, reprogramming prone, profile, and we identify SOX15 from their oocyte-related signature as a prominent responsible candidate. SOX15 orchestrates an efficient oocyte-based reprogramming combination when overexpressed with the also oocyte-enriched histone chaperone ASF1A and OCT4 and, through specific mechanism, generates iPSCs with distinguishable pluripotent state that further present higher differentiation capacity than canonical iPSCs. Our work supports the presence of different pluripotency states in reprogramming and the importance of using metaphase-II oocyte and MnSCs information to provide alternative reprogramming combinations and, importantly, to improve and understand pluripotency acquisition.
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•MnSC expression signature reveals SOX15 as a crucial oocyte-enriched reprogramming factor•SOX15 orchestrates an efficient oocyte-based reprogramming combination in MnSC•Oocyte-based reprogrammed iPSCs (AOX15) show distinct pluripotent state•AOX15 iPSCs present higher differentiation capacity than OSKM-iPSCs
Molecular Biology; Stem Cells Research; Transcriptomics