Abstract

crypt. By 24 hours, tdTomato epifluorescence was observed in Paneth (α-defensin 5+), transit-amplifying cells (Ki67+) and scattered enterocytes (DPP IV+) throughout the villus. Colocalization studies revealed that the tdTomato fluorescent cells were not enteroendocrine (Chromogranin A+), tuft (DCAMKL1+), or goblet cells (Mucin 2+) at the 24h time point in the intestine. Additionally, we analyzed Zfp148 promoter activity in secretory progenitor cells by MATH1 staining and found that these cells also did not express tdTomato fluorescence. By 3 weeks post TX treatment, long tracts of cells were labeled along the length of the villi in addition to persistent and more intense tdTomato fluorescence occurring at the crypt base. In the colon, activated cells gave rise to scattered non-adjacent glands that were completely labeled with tdTomato fluorescence. Conclusion: Zfp148 gene expression (ZBP89) occurred in cells at the intestinal crypt base that morphologically coincide with cells involved in the stem cell niche. Over time these cells were able to propagate and label entire colonic glands and, in the intestine, a majority of the intestinal villus. Although a ubiquitous protein, Zfp148 gene expression is more robust in the stem cell niche implicating a role for this transcription factor in modulating stem cell fate.

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