RNA Sequencing of Lung in an Antenatal Glucocorticoid-Rescued Pulmonary Immaturity Murine Model Reveals Roles for Surfactant Protein B (SPB) and Corticotropin Releasing Hormone (CRH).
Bibliographic record
Abstract
Despite extensive clinical use, the mechanisms by which in utero glucocorticoids promote fetal lung maturity are not well understood. We hypothesized that whole transcriptome shotgun sequencing (RNA-Seq) in biologically relevant models would reveal potential gene pathways by which glucocorticoids antenatally function. We previously reported that in our Erk3-/- MAP kinase family knockout mouse model, 0.4mg/kg dexamethasone administered at E16.5 and E17.5 rescued pulmonary immaturity (decreased sacculation and increased type II pneumocyte glycogen). To significantly expand this work, high integrity (>8.5, Agilent bioanalyzer) coding 3' polyadenylated mRNA was extracted from flash-frozen lung E18.5, and sequencing libraries were generated from random-hexamer synthesized cDNA. <400bp fragmented cDNAs served as sequencing template (Illumina GAII). Transcriptome alignment was against the murine reference genome (NCBI 37), and Cuffdiff software was used to infer expression level. IUGR Erk3-/- neonatal mice died within 24 hours from acute respiratory failure; in utero dexamethasone rescued histological lung maturation and differentiation of type II cells but not neonatal lethality. Employing RNA-Seq, 114 million sequence reads were mapped to the reference genome. Following in silico subtractive hybridization and extensive data mining, two significant glucocorticoid-induced signature pathways in the neonatal lung emerged (B): corticotropin (CRH, CRH receptor 2, urocortin) and surfactants (SPB but not SPA). Biological replicates validated these observations. Antenatal glucocorticoids decrease pulmonary CRH in an Erk3-independent pathway (i.e., histologic type II maturation), and increase Erk3-dependent SPB (i.e., functional pulmonary maturation). Our unbiased RNA shotgun sequencing of fetal signature pathways reveals a previously undescribed role for Erk3, CRH and SPB in fetal pulmonary maturation. (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 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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".