Diverse partial reprogramming strategies restore youthful gene expression and transiently suppress cell identity

Partial pluripotent reprogramming can reverse features of aging in mammalian cells, but the impact on so-matic identity and the necessity of individual reprogramming factors remain unknown. Here, we used sin-gle-cell genomics to map the identity trajectory induced by partial reprogramming in multiple murine cell types and dissected the influence of each factor by screening all Yamanaka Factor subsets with pooled sin-gle-cell screens. We found that partial reprogramming restored youthful expression in adipogenic and mesenchymal stem cells but also temporarily suppressed somatic identity programs. Our pooled screens re-vealed that many subsets of the Yamanaka Factors both restore youthful expression and suppress somatic identity, but these effects were not tightly entangled. We also found that a multipotent reprogramming strat-egy inspired by amphibian regeneration restored youthful expression in myogenic cells. Our results suggest that various sets of reprogramming factors can restore youthful expression with varying degrees of somatic identity suppression. A record of this paper's Transparent Peer Review process is included in the supple-mental information.

Automated summary

Partial pluripotent reprogramming can reverse features of aging in mammalian cells but may temporarily suppress somatic identity programs. Different subsets of the Yamanaka Factors can restore youthful expression and suppress somatic identity to varying degrees. A multipotent reprogramming strategy inspired by amphibian regeneration can restore youthful expression in myogenic cells.