BMAL1 and MEX3A co-regulate intestinal stem cell succession
Chang, F.-P.; Wang, C.-K.; Chou, Y.-C.; Chen, T.-J.; Wu, Y.-W.; Sridharan, S.; Hsu, P.-H.; Hwang-Verslues, W. W.
Show abstract
Chemotherapeutic agents, such as 5-fluorouracil (5-FU), often induce intestinal mucositis due to toxicity to rapidly dividing intestinal stem cells (ISCs). Drug delivery at different times of day can alter 5-FU toxicity; however, the underlying biology is unclear. We found that homeostasis and succession between two ISC types, fast proliferating Lgr5+ crypt base columnar (CBC) cells and stress-resistant +4 cells (Bmi1+), are controlled by the circadian clock transcription factor BMAL1 and the BMAL1-regulated RNA-binding protein MEX3A via both direct transcriptional regulation and post-transcriptional control of Lgr5 mRNA stability. Bmal1 knockout in Lgr5+ CBCs reduced MEX3A expression and CBC numbers but increased Bmi1 expression in the crypts. Timing 5-FU delivery when crypt cells had low Lgr5 but peak level of Bmi1 protected ISCs from apoptosis. Together, these findings identify a novel role of BMAL1 in ISC homeostasis and provide a biological explanation for chronotherapeutic chemoprotection.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Loss of PI3-kinase activity of inositol polyphosphate multikinase impairs PDK1-mediated AKT activation, cell migration, and intestinal homeostasis 94%
- Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis. 93%
- The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains 93%
Similar papers in this journal
Similar papers in this journal
- GFAP-directed Inactivation of Men1 Exploits Glial Cell Plasticity in Favor of Neuroendocrine Reprogramming 93%
- Fmo5 plays a sex-specific role in goblet cell maturation and mucus barrier formation 93%
- GATA4 regulates epithelial morphogenesis in the developing mouse stomach to promote establishment of a glandular columnar epithelium 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.