A136 THE ROLE OF KERATIN-19 POSITIVE STEM CELLS IN COLONIC REGENERATION POST COLITIS
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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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".