A136 THE ROLE OF KERATIN-19 POSITIVE STEM CELLS IN COLONIC REGENERATION POST COLITIS
Why this work is in the frame
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Bibliographic record
Abstract
The intestinal and colonic epithelia are rapidly renewed every 3 to 5 days. In the intestine, at least two principal stem cell pools, comprised of rapidly cycling crypt based columnar (CBC) Lgr5+ cells and slower cycling Bmi1-expressing cells located above the crypt base, have been described. In the colon, however, we have recently identified an additional, spatially distinct, Lgr5-negative stem cell pool that is a subset of Krt19-positive cells. Recent studies have shown that colonic inflammation resulting from DSS-induced colitis leads to loss of distal colonic crypts associated with the rapid loss of Lgr5+ cells. Despite the transient loss of Lgr5+ stem cells, the colonic crypts regenerate and homeostasis is restored. The goal of this study was to determine whether the Krt19+ colonic stem cell pool is responsible for colonic crypt regeneration during colitis. To examine whether Lgr5 and/or Krt19 mark normal colonic stem cells that contribute to epithelial regeneration upon colonic injury, we crossed Lgr5-GFP-IRES-CreER or Krt19-BAC-CreER transgenic mice to the ROSA26r-Tdtomato reporter line. Mice were then treated with tamoxifen followed by water (control) or DSS (in the drinking water x 7 days) to induce colitis. Lgr5+ and Krt19+ cells were then studied in the context of normal homeostasis or following colonic injury following DSS injury. Our results demonstrated that Lgr5+ stem cells are sensitive to DSS-induced colonic injury. Similar DSS-induced colitis injury experiments were also carried out using Notch1-CreER and Math1-CreER transgenic mice crossed to ROSA26r-Tdtomato mice and revealed little to no lineage tracing from absorptive or secretory cells, respectively. In contrast, Krt19 marked long-lived cells above the crypt base that were resistant to DSS-induced colonic epithelial injury and gave rise to Lgr5+ cells in the newly regenerated crypts. Moreover, in separate experiments using Lgr5-DTR-GFP;K19-BAC-CreER; ROSA26r-Tdtomato mice, diphtheria toxin induced ablation of Lgr5+ cells demonstrated that Lgr5+ stem cells are dispensable for colonic epithelial regeneration following DSS-induced colitis. Our data suggest that analogous to the small intestine, Krt19+ stem cells in the colon are similarly more resistant to epithelial injury than Lgr5+ stem cells. CIHR
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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 | 0.000 |
| 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) | 0.000 | 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 it