ArticleThe EMBO journal2021
Identification of a dynamic gene regulatory network required for pluripotency factor-induced reprogramming of mouse fibroblasts and hepatocytes.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The trial behind it
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Conserved Partial Reprogramming Effects on the Methylome.Epigenomes · 2026Article
- A cross-talk between p16High senescence and cellular reprogramming.Clinical science (London, England : 1979) · 2026Review
- The Regulatory Role of mCells · 2026Review
- The regulatory architecture of the primed pluripotent cell state.Nature communications · 2025Article
- An Unbiased Approach to Identifying Cellular Reprogramming-Inducible Enhancers.International journal of molecular sciences · 2024Article
- The occurrence and development of induced pluripotent stem cells.Frontiers in genetics · 2024Review
- Inactivation of Tumor Suppressor CYLD Inhibits Fibroblast Reprogramming to Pluripotency.Cancers · 2023Article
- Article
- Systematic mapping and modeling of 3D enhancer-promoter interactions in early mouse embryonic lineages reveal regulatory principles that determine the levels and cell-type specificity of gene expression.bioRxiv : the preprint server for biology · 2023Article
- Combinatorial targeting of a specific EMT/MET network by macroH2A variants safeguards mesenchymal identity.PloS one · 2023Article
- Global and precise identification of functional miRNA targets in mESCs by integrative analysis.EMBO reports · 2022Article
- Double-Gene Copromoting Expression Analysis in tPA/GH Transgenic Goat Mammary Epithelial Cells and Thrombolytic Activity of tPA In Vitro.BioMed research international · 2022Article
- Review
- Identification of a dynamic gene regulatory network required for pluripotency factor-induced reprogramming of mouse fibroblasts and hepatocytes.The EMBO journal · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The generation of induced pluripotent stem cells (iPSCs) from somatic cells provides an excellent model to study mechanisms of transcription factor-induced global alterations of the epigenome and genome function. Here, we have investigated the early transcriptional events of cellular reprogramming triggered by the co-expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) in mouse embryonic fibroblasts (MEFs) and mouse hepatocytes (mHeps). In this analysis, we identified a gene regulatory network composed of nine transcriptional regulators (9TR; Cbfa2t3, Gli2, Irf6, Nanog, Ovol1, Rcan1, Taf1c, Tead4, and Tfap4), which are directly targeted by OSKM, in vivo. Functional studies using single and double shRNA knockdowns of any of these factors caused disruption of the network and dramatic reductions in reprogramming efficiency, indicating that this network is essential for the induction and establishment of pluripotency. We demonstrate that the stochastic co-expression of 9TR network components occurs in a remarkably small number of cells, approximating the percentage of terminally reprogrammed cells as a result of dynamic molecular events. Thus, the early DNA-binding patterns of OSKM and the subsequent probabilistic co-expression of essential 9TR components in subpopulations of cells undergoing reprogramming steer the reconstruction of a gene regulatory network marking the transition to pluripotency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.