Hypoxia inducible factor (HIF)‐2α is required for the development of the catecholaminergic phenotype of sympathoadrenal cells
Bibliographic record
Abstract
The basic helix-loop-helix transcription factor, hypoxia inducible factor (HIF)-2alpha has been implicated in the development of the catecholaminergic phenotype in cells of the sympathoadrenal (SA) lineage; however, the underlying mechanisms and HIF-2alpha targets remain unclear. Using an immortalized rat adrenomedullary chromaffin cell line (MAH cells) derived from a fetal SA progenitor, we examined the role of HIF-2alpha in catecholamine biosynthesis. Chronic hypoxia (2% O(2), 24 h) induced HIF-2alpha in MAH cells but expression of the rate-limiting enzyme, tyrosine hydroxylase (TH) and catecholamine levels were unaltered. Interestingly, HIF-2alpha depleted MAH cells showed dramatically lower (5-12 times) levels of dopamine and noradrenaline compared with wild-type and scrambled controls, even in normoxia (21% O(2)). This was correlated with a marked reduction in the expression of DOPA decarboxylase (DDC) and dopamine beta hydroxylase (DbetaH) but not TH. Chromatin immunoprecipitation assays revealed that HIF-2alpha was bound to the DDC gene promoter which contains two putative hypoxia response elements. These data suggest that a basal level of HIF-2alpha function is required for the normal developmental expression of DDC and DbetaH in SA progenitor cells, and that loss of this function leads to impaired catecholamine biosynthesis.
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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) | 0.001 | 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".