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SMAD2/3 potentiate cell identity conversions with master transcription factors

ABSTRACT: The exogenous expression of master transcription factors (TFs) is a powerful and exciting approach to convert cellular identity. Yet, the generation of desired cell types is often plagued by inefficiency, slow kinetics and inability to produce mature cell types. Through investigations of the molecular mechanisms of induced plurpipotent stem cell generation, we discovered that expression of constitutively active Smad2/3 (Smad2CA/3CA), together with the Yamanaka factors, could dramatically improve the efficiency and kinetics of reprogramming. Mechanistically, SMAD3 interacted with both co-activators and reprogramming factors, bridging their interaction during reprogramming. Fascinatingly, SMAD2/3 interact with a multitude of master TFs in different cell types, and conversions of B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons were also markedly enhanced when their master TFs were co-expressed with Smad3CA. These results revealed the existence of shared molecular mechanisms underlying diverse TF-mediated cellular conversions, and demonstrated SMAD2/3 as a widely applicable booster.

ORGANISM(S): Mus musculus

PROVIDER: GSE72596 | GEO | 2017/11/03

SECONDARY ACCESSION(S): PRJNA294432

REPOSITORIES: GEO

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