Abstract 9127: C-myb-regulated Expression Of Mir-143/145 In Embryonic Stem Cell-derived And Adult Vascular Smooth Muscle Cells
Bibliographic record
Abstract
Background: The c-myb gene encodes for the transcription factor c-Myb, which has been implicated in the differentiation of vascular smooth muscle cells (VSMCs) from neural crest and embryonic stem cells (ESCs). Mouse ESCs lacking c-myb (KO) failed to express SMC-specific genes and did not differentiate into contractile SMCs in embryoid bodies (EB), with c-Myb regulating the formation of a specific Flk-1+/PDGFRα- (F+/P-) progenitor of VSMCs. Others showed that expression of the miR-143/145 cluster is restricted to adult SMC lineages and promotes the expression of contractile genes. Hypothesis: c-Myb mediates the transcriptional regulation of miR-143/145. Methods &Results : Flow-sorting of cardiovascular-directed d3.75 EBs showed high levels of miR-143/145 expression in F+/P- (c-myb high) cells, with low levels in other (c-myb low: F+/P+ and F-/P+) cell populations. Importantly, no differences in the expression levels of miR-143/145 could be detected in F+/P-, F-/P+ and F+/P+ cells derived from c-myb KO EBs. Multiple putative c-Myb consensus-binding sites (conserved in human and mouse) were identified in 3kb and 20kb enhancers upstream of the miR-143/145 cluster. Chromatin immunoprecipitation assays in both cardiovascular-directed d3.75 EBs and immortalized mouse adult aortic SMCs (MOVAS) revealed c-Myb binding to multiple specific sites. Next, c-Myb responsiveness of wild-type and deletion mutant enhancer-reporter constructs was assayed in HEK293 cells. These studies confirmed two c-Myb-dependent miR-143/145 enhancer activities. Conclusion: Our data suggest that c-Myb-regulated VSMC differentiation and contractile gene expression may be mediated by direct binding to specific transcription enhancer elements in the miR-143/145 cluster. *Authors have contributed equally to this work.
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.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".