β‐catenin in the kidney stroma modulates pathways and genes that regulate kidney development
Bibliographic record
Abstract
Kidney development is dependent on proper cell communication between the epithelial, mesenchymal and stromal cell lineages. Recent studies by our laboratory, and others, demonstrate that the renal stroma, a population of fibroblast‐like cells, is required for proper collecting duct and nephron formation. However, how the renal stroma communicates with other cell lineages and contributes to proper kidney development is not well known. β‐catenin is a multifunctional protein involved in cell adhesion and transcriptional regulation. Our previous work demonstrated that stromal β‐catenin alters gene expression and the development of the neighbouring epithelial and mesenchymal cells. However, how stromal β‐catenin regulates stromal communication with the other cell lineages is not well established. We hypothesize that stromal β‐catenin modulates genes and signaling pathways that mediate this cellular communication. To address this hypothesis, we generated mouse models with β‐catenin deficiency ( β‐cat stroma(def) ) or overexpression ( β‐cat stroma(over) ) exclusively in the renal stroma. Wild‐type, β‐cat stroma(def) and β‐cat stroma(over) stromal cells were isolated at E12.5 and E13.5 via fluorescence activated cell sorting (FACS) and were verified by quantitative RT‐PCR to be a pure population of stroma cells. The isolated stromal cells then underwent RNA sequencing (RNA‐seq). The RNA‐seq analysis identified 93 biological processes that were down‐regulated in β‐cat stroma(def) cells at E12.5 and E.13.5, and 491 biological processes that were up‐regulated in β‐cat stroma(over) cells at E12.5 and E13.5. Interestingly, 76% of the biological pathways that were down‐regulated in the β‐cat stroma(def) model at both E12.5 and E13.5 were also up‐regulated in the β‐cat stroma(over) at both time points, strongly suggesting that they are regulated by β‐catenin. Of particular interest to our research were the biological processes that were significantly modulated by stromal β‐catenin and are associated with key kidney developmental processes. Specifically, 8 processes linked to Wnt signaling, 16 processes linked to branching morphogenesis, 5 processes linked to nephrogenesis, and 15 processes linked to angiogenesis. Select differentially expressed candidate genes from these biological pathways were validated by immunohistochemistry, immunofluorescence, or in situ hybridization at E12.5 and E13.5. The RNA‐seq also identified numerous novel candidate β‐catenin target genes with undefined roles in kidney development. Novel genes that were most significantly down‐regulated in the β‐cat stroma(def) cells and/or up‐regulated in the β‐cat stroma(over) at both E12.5 and E13.5 included Emilin2, Atrnl1, Car3, Apcdd1, LHFP, Pitx1, Npy1r, Sttb3, Mctp2, Nkd2, Man1a and Car13 . In conclusion, our results support that stromal β‐catenin plays a significant role in regulating multiple major kidney developmental processes, including branching morphogenesis, nephrogenesis and angiogenesis. Support or Funding Information NSERC, CIHR, KFOC
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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".