A7 FOXL1+ TELOCYTES IN MOUSE COLON ORCHESTRATE ECM BIODYNAMICS AND WOUND REPAIR RESOLUTION
Bibliographic record
Abstract
Abstract Background The extracellular matrix (ECM) is a complex assembly of proteins that provide mechanical and biochemical stimuli to the epithelial and mesenchymal cells of the GI mucosa. Deficiencies in ECM assembly, protein production or excessive accumulation can lead to multiples pathologies including fibrosis and cancer. FoxL1+-Telocytes (TCFoxL1+) are subepithelial cells that form a network underneath the epithelium, contributing to the microenvironment that supports epithelial and immune cell homeostasis. We have previously shown that BMPR1A signaling deletion in TCFoxL1+ influences the microenvironment via stromagenesis, immune infiltration and colonic dysplasia in mouse model of GI diseases. However, the precise molecular and mechanical events that contributes to the onset of this state have yet to be elucidated. Aims Characterize the modulations in ECM biodynamics induced by BmpR1a-deficient TC FoxL1+ ( BmpR1a△FoxL1+) in mouse colon submucosa. Methods Matrisomics was performed to determine the inventory of ECM proteins expressed solely in the GI stromal compartment following tissue deconstruction of control and BmpR1a△FoxL1+ mice colons. Histological and biochemical methods were used to further characterize the collagen network and matrisome-associated modulations. Fluorescence In Situ Hybridization (FISH) was performed to study the bacterial presence in the mucosa. Results The set of identified proteins shows an enrichment for proteins involved in collagen network regulation, wound repair homeostasis and immune regulation such as Col1a2, Col3a1, Col6a4 and Coll14a1, as well as SerpinH1, MFAP4, ANXA1 and S100A9. Collagen network is affected with increased deposition and reorganization of fiber alignment. Unfolded collagen content was also increased in dysplastic areas of BmpR1a△FoxL1+ mouse colon with a concomitant increase in the collagen-chaperone SerpinH1. Validations of other targets indicate that BmpR1a△FoxL1+ mice deals with some type of tissue micro-injury and inflammation that is unresolved, creating a unfavorable microenvironment for tissue homeostasis. Conclusions Taken together, these results suggest that Bmp-signaling deficient TCFoxL1+ significantly contribute to the collagen network biodynamics through increased collagen deposition, fiber alignment reorganization and regulation of the collagen triple-helix assembly. Other matrisome modulations suggest a state of unresolved wound healing due to tissue injury, that could be the etiology of GI pathology and lead to more severe conditions upon various environmental triggers. Funding Agencies CIHR
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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) | 0.003 | 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".