Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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- Teacher spread
- 0.279 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
Ectopic expression of defined transcription factors can reprogram somatic cells to induced pluripotent stem (iPS) cells, but the utility of iPS cells is hampered by the use of viral delivery systems. Small molecules offer an alternative to replace virally transduced transcription factors with chemical signaling cues responsible for reprogramming. In this report we describe a small-molecule screening platform applied to identify compounds that functionally replace the reprogramming factor Klf4. A series of small-molecule scaffolds were identified that activate Nanog expression in mouse fibroblasts transduced with a subset of reprogramming factors lacking Klf4. Application of one such molecule, kenpaullone, in lieu of Klf4 gave rise to iPS cells that are indistinguishable from murine embryonic stem cells. This experimental platform can be used to screen large chemical libraries in search of novel compounds to replace the reprogramming factors that induce pluripotency. Ultimately, such compounds may provide mechanistic insight into the reprogramming process.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
The record
- Venue
- Proceedings of the National Academy of Sciences
- Topic
- Pluripotent Stem Cells Research
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- —
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of General Medical SciencesCanadian Institutes of Health ResearchSkaggs Institute for Chemical Biology, Scripps Research InstituteNovartis FoundationNational Cancer InstituteNational Institutes of HealthNational Science Foundation
- Keywords
- ReprogrammingKLF4Induced pluripotent stem cellHomeobox protein NANOGEmbryonic stem cellCell biologySOX2BiologyTranscription factorStem cellSomatic cellCellGeneticsGene
- Has abstract in OpenAlex
- yes