Bibliographic record
Abstract
Each human kidney contains approximately 1 million glomeruli that filter the blood, removing excess fluid and small solutes from the body. Glomeruli are formed from metanephric mesenchymal cells that have been induced by adjacent ureteric bud epithelium. In the mature kidney, the glomerular filtration barrier (GFB) consists of highly specialized glomerular epithelial cells (podocytes), fenestrated endothelial cells and an intervening glomerular basement membrane. Over the past two decades, genetic targeting in mice has provided great insight into the function of many genes in glomerular development and disease. In our lab, we have identified a transcription factor known as Tcf21 that is expressed in presumptive and mature podocytes. Through standard gene targeting, we showed that Tcf21 is required for terminal differentiation of podocytes, ingrowth of glomerular capillaries and formation of a functional GFB. We have also generated a number of genetic tools that enable temporally and spatially controlled deletion or over‐expression of genes in specific cell compartments of the glomerulus. Using this approach, we have shown that crosstalk between the podocyte and glomerular endothelium is critical for development and maintenance of the GFB. One major player in these interactions is the angiogenic factor, VEGF‐A. During development there is exquisite dosage sensitivity to this factor, as increasing reductions in VEGF‐A produced by the podocyte lead to more severe defects in the endothelial compartment. Conversely, upregulation of the major VEGF‐164 isoform in developing or mature glomeruli leads to marked and rapid changes in glomerular permeability. Podocyte‐selective stabilization of the hypoxia inducible factors that regulate VEGF‐A leads to an explosive onset of crescentic glomerular disease, podocyte proliferation and death due to renal failure. Taken together, these results demonstrate the power of mouse genetics to study glomerular biology, emphasize that podocytes function as vasculature support cells and provide preclinical models for renal disease.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.004 | 0.004 |
| Insufficient payload (model declined to judge) | 0.025 | 0.006 |
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".