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Fate mapping in mouse demonstrates early secretory differentiation directly from Lgr5+ intestinal stem cells

GSE241524 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/12/06 Platform GPL30172
Summary
The intestinal epithelium has a remarkably high turnover in homeostasis. It remains unresolved how turnover is orchestrated at the cellular level and how the behaviour of stem and progenitor cells ensures tissue maintenance. To address this, we combined quantitative fate mapping in three complementary mouse models with mathematical modelling and single-cell RNA sequencing. Our integrated approach generated a spatially and temporally defined model of crypt maintenance that is based on two cycling populations: crypt-based columnar (CBC) and transit amplifying (TA) cells. Validation experiments substantiated the predictions from the model revealing TA cells as the major contributor to the absorptive lineage, while balanced CBC cell fate choices controlled the numbers of cells in the secretory lineage. By unravelling these mechanisms, we gain insights into the process of tissue turnover and provide direct evidence to support the notion of CBC cells as the major driver of the intestinal epithelium replenishment.
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Direct links to NCBI, no account and no request form: the whole study as GSE241524_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1008581 and SRA study SRP456685. Searching any of these in the dataset finder brings you back here.

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