Investigating colonic lymphatic endothelial cell (LEC) heterogeneity in homeostasis and disease pathogenesis 3727
Bibliographic record
Abstract
Abstract Description The pathophysiology of ulcerative colitis (UC) is driven by a disrupted intestinal barrier that triggers aberrant immune responses to gut commensal microbes. The lymphatic vasculature is critical for maintaining intestinal immune homeostasis, and lymphatic expansion is a hallmark of UC pathology. However, the molecular drivers and functional consequences of increased lymphangiogenesis remain unclear. During development, PROX1+/LYVE1+ lymphatic endothelial cell (LEC) progenitors originating from the cardinal vein form a mature lymphatic network through sprouting lymphangiogenesis. We recently showed that lymphatic vessels in the colonic mucosa run along the base of the crypts, extending into individual mucosal folds, and begin developing shortly after birth. High resolution imaging of colons from newborn pups revealed PROX1+/LYVE1+ mesenteric lymphatic vessels beginning to invade the wall of the colon and several individual PROX1+/LYVE1- LECs dispersed throughout the mucosa. By day 2, these LECs appeared near the growing mucosal fold lymphatics extending from the mesentery. These data suggest that the colon LECs are heterogenous in origin and we hypothesize that the distinct LEC populations exhibit unique spatial patterns, gene expression and functions in the colon. This study aims to describe the functional consequences of colonic LEC heterogeneity under homeostatic and inflammatory conditions with the goal of identifying new therapeutic targets for treatment of UC. Funding Sources NIH NIAD grant U01AI163064 Topic Categories Mucosal and Regional Immunology (MUC)
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".