Cell population kinetics in the mouse jejunal crypt

Intestinal Stem Cell Replacement Follows a Pattern of Neutral Drift

“…Nevertheless, experimental studies of the fitness effects of defined single-point mutations have proven useful, because they allow an assumption-free determination of the underlying DFE, including the frequencies of strongly deleterious mutations. A few such studies in viruses have demonstrated a bimodal DFE, with most mutations being either neutral or lethal (13,20,21).…”

“…2, as its effect would be resolved rapidly compared to one-dimensional drift around the crypt circumference (SOM S-III.4). If we estimate the number of stem cells on the basis of the total number of Bmi1 + and Lgr5 + cells (4, 5, 19), we can conclude that their total number is >16, suggesting that stem cells are replaced laterally by their neighbors at a rate l ≈ 1 per day comparable to the measured cell division rate (5,(20)(21)(22). Therefore, asymmetric cell division is not the sole, or even the most common, mode of stem cell division in the intestine: Symmetric stem cell division is not a rare event, but is a central aspect of homeostasis.…”

Transcriptional Integration of Distinct Microbial and Nutritional Signals by the Small Intestinal Epithelium

“…Colonization of GF mice has leads to transcriptional responses that remain dynamic for up to 30 days and are dependent on the composition of the microbial community (El Aidy et al 2012;El Aidy et al 2013). Simultaneously, the intestinal epithelial layer turns over every 3-5 days with the potential to alter IEC subtypes and crypt-villus architecture while simultaneously making acute transcriptional changes on the order of minutes (Cheng and Leblond 1974;Al-Dewachi et al 1975;El Aidy et al 2013;Mah et al 2014;Nyima et al 2016;Shamir et al 2016;Zeituni et al 2016;Haber et al 2017;Mucunguzi et al 2017;Xie et al 2020;Heppert et al 2021). We aimed here to understand how the intestine integrates two distinct conditions simultaneously, and specifically how microbes modify the response to a high fat meal.…”

“…Condition specific H3K27ac changes are restricted to enterocyte-and ISC-specific regulatory regions and impacted by Hnf4a binding Since 2h after a HFM is likely too soon to induce major changes in IEC cell-type abundance (Cheng and Leblond 1974;Al-Dewachi et al 1975), the enrichment of HNF4A motifs in GF+HFM (Fig. 4N-Q) and differential utilization of enterocyte and ISC regulatory regions in +HFM-up conditions (Fig.…”

Intestinal villus structure contributes to even shedding of epithelial cells

“…Each villus is surrounded by several invagina-tions called crypts. Intestinal stem cells at the crypt base divide with cell cycles of $12-24 h (10,11). Daughter cells differentiate within the crypts, then ascend the crypts, and then migrate to the nearest villus.…”