Retinoic acid enhances germ cell differentiation of mouse skin-derived stem cells
Bibliographic record
Abstract
BACKGROUND: Retinoic acid (RA) signaling has been identified as a key driver in male and female gamete development. The presence of RA is a critical step in the initiation of meiosis and is required for the production of competent oocytes from primordial germ cells. Meiosis has been identified as a difficult biological process to recapitulate in vitro, when differentiating stem cells to germ cells. We have previously shown that primordial germ cell-like cells, and more advanced oocyte-like cells (OLCs), can be formed by differentiating mouse skin-derived stem cells. However, the OLCs remain unable to function due to what appears to be failure of meiotic initiation. The aim of this study was to determine the effect of RA treatment, during stem cell differentiation to germ cells, particularly on the initiation of meiosis. RESULTS: Using qPCR we found significant increases in the meiosis markers Stra8 and Sycp3 and a significant reduction in the meiosis inhibitor Nanos2, in the differentiating populations. Furthermore, OLCs from the RA treated group, expressed significantly more of the meiosis regulatory gene Marf1 and the oocyte marker Oct4. At the protein level RA treatment was found to increase the expression of the gap junction protein CX43 and the pluripotency marker OCT4. Moreover, the expression of SYCP3 was significantly upregulated and the localization pattern better matched that of control fetal ovarian cells. RA treatment also improved the structural integrity of the OLCs produced by initiating the expression of all three zona pellucida transcripts (Zp1-3) and improving ZP3 expression levels and localization. Finally, the addition of RA during differentiation led to an almost two-fold increase in the number of OLCs recovered and increased their in vitro growth. CONCLUSION: RA is a key driver in the formation of functioning gametes and its addition during stem cell to germ cell differentiation improves OLCs entry into meiosis.
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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 | 0.003 | 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 | 0.001 |
| 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".