Molecular Evidence for OCT4-Induced Plasticity in Adult Human Fibroblasts Required for Direct Cell Fate Conversion to Lineage Specific Progenitors
Bibliographic record
Abstract
Here we characterize the molecular and biological requirements for OCT4 plasticity induction in human skin derived fibroblasts (hFibs) that allows direct conversion of cell fate without iPSC formation. Our results indicate that adult hFibs not only require OCT4 but also short-term exposure to reprogramming media (RM) to successfully undergo direct conversion to early hematopoietic and neural progenitor fates. RM was found to be essential in this process and allowed for unique changes in global gene expression specific to the combined effects of OCT4 and treatment with reprogramming media to establish a plastic state. This molecular state of hFib plasticity was distinct from transient expression of a full complement of iPSC reprogramming factors consistent with a lack in molecular hallmarks of iPSC formation. Human Fib-derived OCT4 plastic cells display elevated levels of developmentally related genes associated with multiple lineages, but not those associated with pluripotency. In response to changes in the extracellular environment, plastic OCT4-expressing hFibs further activate genes involved in hematopoietic as well as tripotent neural progenitor biology that allow cell fate conversion. Our study provides a working definition of hFib-induced plasticity using OCT4 and a deconvoluted system to elucidate the process of direct cell fate reprogramming.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".