Direct lineage conversions: unnatural but useful?
Open accessAbstract
Classic experiments such as somatic cell nuclear transfer into oocytes and cell fusion demonstrated that differentiated cells are not irreversibly committed to their fate. More recent work has built on these conclusions and discovered defined factors that directly induce one specific cell type from another, which may be as distantly related as cells from different germ layers. This suggests the possibility that any specific cell type may be directly converted into any other if the appropriate reprogramming factors are known. Direct lineage conversion could provide important new sources of human cells for modeling disease processes or for cellular-replacement therapies. For future applications, it will be critical to carefully determine the fidelity of reprogramming and to develop methods for robustly and efficiently generating human cell types of interest.
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Somatic cells can be induced to de-differentiate to an ESC-like phenotype by forcing expression of specific transcription factors; these iPSCs are donor-specific and phenotypically highly similar to ESCs.
“Somatic cells can be induced to de-differentiate to an Embryonic Stem Cell (ESC)-like phenotype by forcing the expression of specific transcription factors; these cells, termed Inducible Pluripotent Stem Cells (iPSCs), are donor-specific and phenotypically highly similar to ESCs (511).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [511]
The Introduction (page unavailable) says four transcription factors can reprogram somatic cells to a pluripotent state, and Potential applications for basic research and medicine (page unavailable) describes patient-derived iPS cells. But the Introduction presents a return to a developmental ground state as a possibility, not an established de-differentiation mechanism; the copy also does not establish that iPSCs are phenotypically highly similar to ESCs. (LLM, conf=0.85)
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- Authors
- Vierbuchen, T., & Wernig, M.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Wernig, Marius
- Venue
- Nature Biotechnology
- Published
- 2011-10
- Volume
- 29
- Issue
- 10
- Pages
- 892-907
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC3222779
- OpenAlex
- W1933400321
- Cited by
- 259
- References
- 34
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 12 · 2020: 10 · 2019: 18 · 2018: 16 · 2017: 12 · 2016: 28 · 2015: 21 · 2014: 31 · 2013: 47 · 2012: 38
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH092931)
- National Institute of Neurological Disorders and Stroke (RC4NS073015)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- cellular reprogramming, somatic cell nuclear transfer, cell fusion, induced pluripotent stem cells, transdifferentiation, reprogramming factors, disease modeling
- MeSH terms
- Animals, Endoderm, Humans, Organ Specificity, Cell Lineage, Biomedical Research, Epigenesis, Genetic, Cellular Reprogramming
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