Identification of Bone Morphogenetic Protein 2 (BMP2)-Regulated Genes in Gonadotrope (LbetaT2) Cells.
Bibliographic record
Abstract
Pituitary follicle-stimulating hormone (FSH) synthesis is regulated by proteins in the transforming growth factor beta (TGFbeta) superfamily, in particular the activins and inhibins. We recently reported that other TGFbeta ligands, bone morphogenetic proteins (BMPs) 2 and 4, can stimulate transcription of the FSHbeta subunit (Fshb) alone and synergistically with activins. We further showed that BMP2 signals via the type I receptor BMPR1A (or ALK3) to mediate its effects; however, the intracellular mechanisms through which BMP2 regulates Fshb are currently unknown. We therefore used microarray analyses (Affymetrix 430 v.2.0 GeneChips) to identify BMP2 target genes in the murine gonadotrope cell line LbetaT2. Cells were treated in duplicate with vehicle or 2 nM BMP2 for 24 h in the presence of the activin type I receptor small molecule inhibitor SB431542 to remove the potentially confounding effects of endogenous activin B signaling in these cells. The raw chip data were analyzed using FlexArray (v. 1.3 from Genome Quebec) and cluster analysis performed with the DAVID online functional annotation tool. BMP2 stimulated a greater than two-fold increase in mRNA levels of 18 genes [including inhibitor of DNA binding 1 (Id1), Id2, Id3, Asgr1, Atp2c2, Chrna2, Ephx1, Evc2, Gdf9, Gkn1, Hesx1, Klk7, Rgs6, Rya3, Smad6, tbc1d10a, Tnni3, and Tnnt1], while down-regulating the levels of seven transcripts by greater than two-fold [Calb1, Camk4, Cpa1, Crym, Matn1, Stk25, and Tg]. A subset of the genes identified on the arrays was selected for validation analyses by quantitative real-time RT-PCR. Twelve of the 13 genes tested showed changes in mRNA expression consistent with the microarray data. We are now examining the potential roles of these genes (and their protein products) in BMP2's independent and synergistic regulation of Fshb. In our initial studies, we focused on the Ids because they were among the most significantly up-regulated genes on the arrays and ID proteins have been implicated as effectors of BMP signaling in a variety of cellular systems. Depletion of endogenous Id2 and Id3, but not Id1, using short-interfering (si) RNAs diminished the synergistic effects of BMP2 and activin A on Fshb transcription. We are currently examining the functional roles, if any, of the other genes identified on the array in BMP2 regulated Fshb transcription. (poster)
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.002 | 0.001 |
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".