ArticleNature cell biology2013
Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT-MET mechanism for optimal reprogramming.
Article in Nature cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 1 of them a synthesis that pooled it.
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Who cites it
129 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Dynamic control of cell state transitions during tissue morphogenesis.The EMBO journal · 2026Review
- Concurrent jamming and mesenchymal-to-epithelial transitions during airway basal stem cell differentiation.iScience · 2026Article
- Spontaneous whole genome duplication renders mouse embryonic fibroblasts resistant to reprogramming.Cell & bioscience · 2026Article
- Cytoplasm-nucleus shuttling of TET2: an intrinsic brake in colorectal cancer progression.Cell death & disease · 2026Article
- MYO1B in human disease: an actin-based motor linking membrane trafficking to oncogenic signaling, metastasis, and vascular aging.Frontiers in oncology · 2026Review
- Epigenetic aging and rejuvenation of the brain: drivers, consequences, and interventions.BMB reports · 2026Review
- Enhanced Activities of OCT4 and SOX2 Promote Epigenetic Reprogramming by Shortening G1 Phase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Stepwise Administration of Bone-Targeted Lipid Nanoparticles Encapsulating Valproic Acid and TUDCA Facilitates In Vivo Direct Reprogramming for Osteoporosis Treatment.Tissue engineering and regenerative medicine · 2025Article
- Amniotic membrane promotes doxorubicin potency by suppressing SH-SY5Y neuroblastoma cell angiogenesis.BMC cancer · 2025Article
- Two distinct epithelial-to-mesenchymal transition programs control invasion and inflammation in segregated tumor cell populations.Nature cancer · 2024Article
- Manipulating cell fate through reprogramming: approaches and applications.Development (Cambridge, England) · 2024Review
- Putative epithelial-mesenchymal transitions during salamander limb regeneration: Current perspectives and future investigations.Annals of the New York Academy of Sciences · 2024Review
- Generation and characterization of giant panda induced pluripotent stem cells.Science advances · 2024Article
- Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer.Cell death and differentiation · 2024Article
- ID2 promotes tumor progression and metastasis in thyroid cancer.Endocrine · 2024Article
- Review
- Retrospective identification of cell-intrinsic factors that mark pluripotency potential in rare somatic cells.Cell systems · 2024Article
- How important is EMT for cancer metastasis?PLoS biology · 2024Article
- Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming.Nature aging · 2024Review
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Present practices for reprogramming somatic cells to induced pluripotent stem cells involve simultaneous introduction of reprogramming factors. Here we report that a sequential introduction protocol (Oct4-Klf4 first, then c-Myc and finally Sox2) outperforms the simultaneous one. Surprisingly, the sequential protocol activates an early epithelial-to-mesenchymal transition (EMT) as indicated by the upregulation of Slug and N-cadherin followed by a delayed mesenchymal-to-epithelial transition (MET). An early EMT induced by 1.5-day TGF-β treatment enhances reprogramming with the simultaneous protocol, whereas 12-day treatment blocks reprogramming. Consistent results were obtained when the TGF-β antagonist Repsox was applied in the sequential protocol. These results reveal a time-sensitive role of individual factors for optimal reprogramming and a sequential EMT-MET mechanism at the start of reprogramming. Our studies provide a rationale for further optimizing reprogramming, and introduce the concept of a sequential EMT-MET mechanism for cell fate decision that should be investigated further in other systems, both in vitro and in vivo.
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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.