ArticleNucleic acids research2014
A transient disruption of fibroblastic transcriptional regulatory network facilitates trans-differentiation.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
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- Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts.Frontiers in immunology · 2023Article
- Single-cell transcriptional profiling informs efficient reprogramming of human somatic cells to cross-presenting dendritic cells.Science immunology · 2022Article
- Inducing human retinal pigment epithelium-like cells from somatic tissue.Stem cell reports · 2022Article
- Regulatory network-based imputation of dropouts in single-cell RNA sequencing data.PLoS computational biology · 2022Article
- Responsiveness to perturbations is a hallmark of transcription factors that maintain cell identity in vitro.Cell systems · 2021Article
- Single-Cell Genomics: Catalyst for Cell Fate Engineering.Frontiers in bioengineering and biotechnology · 2021Review
- Direct cell-fate conversion of somatic cells: Toward regenerative medicine and industries.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2020Review
- Attenuation of PRRX2 and HEY2 enables efficient conversion of adult human skin fibroblasts to neurons.Biochemical and biophysical research communications · 2019Article
- OVOL2 induces mesenchymal-to-epithelial transition in fibroblasts and enhances cell-state reprogramming towards epithelial lineages.Scientific reports · 2019Article
- A positive feedback loop bi-stably activates fibroblasts.Nature communications · 2018Article
- A synthetic DNA-binding inhibitor of SOX2 guides human induced pluripotent stem cells to differentiate into mesoderm.Nucleic acids research · 2017Article
- Asymmetric Regulation of Peripheral Genes by Two Transcriptional Regulatory Networks.PloS one · 2016Article
- Reprogramming barriers and enhancers: strategies to enhance the efficiency and kinetics of induced pluripotency.Cell regeneration (London, England) · 2015Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptional Regulatory Networks (TRNs) coordinate multiple transcription factors (TFs) in concert to maintain tissue homeostasis and cellular function. The re-establishment of target cell TRNs has been previously implicated in direct trans-differentiation studies where the newly introduced TFs switch on a set of key regulatory factors to induce de novo expression and function. However, the extent to which TRNs in starting cell types, such as dermal fibroblasts, protect cells from undergoing cellular reprogramming remains largely unexplored. In order to identify TFs specific to maintaining the fibroblast state, we performed systematic knockdown of 18 fibroblast-enriched TFs and analyzed differential mRNA expression against the same 18 genes, building a Matrix-RNAi. The resulting expression matrix revealed seven highly interconnected TFs. Interestingly, suppressing four out of seven TFs generated lipid droplets and induced PPARG and CEBPA expression in the presence of adipocyte-inducing medium only, while negative control knockdown cells maintained fibroblastic character in the same induction regime. Global gene expression analyses further revealed that the knockdown-induced adipocytes expressed genes associated with lipid metabolism and significantly suppressed fibroblast genes. Overall, this study reveals the critical role of the TRN in protecting cells against aberrant reprogramming, and demonstrates the vulnerability of donor cell's TRNs, offering a novel strategy to induce transgene-free trans-differentiations.
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