1. Requirement of Bccipfor the Regeneration of Intestinal Progenitors
- Author
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Lu, Huimei, Ye, Caiyong, Liu, Jingmei, Rabson, Arnold B., Verzi, Michael, De, Subhajyoti, and Shen, Zhiyuan
- Abstract
BCCIP was originally identified as a BRCA2 and CDKN1A/p21 interaction protein. Although a partial loss of BCCIPfunction is sufficient to trigger genomic instability and tumorigenesis, complete deletion of BCCIPis lethal to cells. Using Rosa26-CreERT2 mouse models, we found that induced Bccipdeletion in adult mice caused an acute intestinal epithelial denudation that cannot be relieved by co-deletion of Trp53. The critical role of Bccipin intestine epithelial renewal was verified with a Villin-CreERT2 mouse model. The epithelium degeneration was associated with a rapid loss of the proliferative capability of the crypt progenitor cells in vivo, lack of crypt base columnar stem cell markers, and a failure of in vitrocrypt organoid growth. RNA-Seq analysis of freshly isolated intestinal crypt cells showed that Bccipdeletion caused an overwhelming down-regulation of genes involved in mitotic cell division but an up-regulation of genes involved in apoptosis and stress response to microbiomes. Our data not only indicate that intestinal epithelium is the most sensitive tissue to whole-body deletion of Bccipbut also point to Bccipas a novel and critical factor for the proliferation of the intestinal progenitors. These findings have significant implications for understanding why a hypomorphic loss of BCCIP functions is more relevant to tumorigenesis.
- Published
- 2021
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