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MTGR1 is required to maintain small intestinal stem cell populations - scRNA sequencing

ABSTRACT: Loss of MTGR1 broadly skews intestinal cell lineages. Here, we used sc-RNA sequencing to analyze MTGR1-dependent changes in intestinal cell and stem cell populations.

ORGANISM(S): Mus musculus

PROVIDER: GSE270545 | GEO | 2024/07/01

REPOSITORIES: GEO

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MTGR1 is required to maintain small intestinal stem cell populations - RNA-sequencing

Project description:Undifferentiated intestinal stem cells (ISCs), particularly those marked by Lgr5, are crucial for maintaining homeostasis and resolving injury. Lgr5+ cells in the crypt base constantly divide, pushing daughter cells upward along the crypt axis where they differentiate into specialized cell types. Coordinated execution of complex transcriptional programs are necessary to allow for the maintenance of undifferentiated stem cells while permitting differentiation of the wide array of intestinal cells necessary for homeostasis. Previously, members of the myeloid translocation gene (MTG) family have been identified as transcriptional co-repressors that regulate stem cell maintenance and differentiation programs in multiple organ systems, including the intestine. One MTG family member, myeloid translocation gene related 1 (MTGR1), has been recognized as a crucial regulator of secretory cell differentiation and response to injury. However, whether MTGR1 contributes to the function of ISCs has not yet been examined. Here, using Mtgr1-/- mice, we have assessed the effects of MTGR1 loss specifically in ISC biology. Interestingly, loss of MTGR1 increased the total number of cells expressing Lgr5, the canonical marker of cycling ISCs, suggesting higher overall stem cell numbers. However, expanded transcriptomic and functional analyses revealed deficiencies in MTGR1 null ISCs, including deregulated ISC-associated transcriptional programs. Ex vivo, intestinal organoids established from Mtgr1 null were found nearly completely unable to survive and expand, likely due to aberrant differentiation and loss of stem and proliferative cells. Together, these results indicate that MTGR1’s role in intestinal differentiation is likely to be stem cell intrinsic and identify a novel role MTGR1 in maintaining ISC function.

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MTGR1 is required to maintain small intestinal stem cell populations - scRNA sequencing

Project description:MTGR1 is required to maintain small intestinal stem cell populations - scRNA sequencing

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MTGR1 is required to maintain small intestinal stem cell populations - RNA-sequencing

Project description:MTGR1 is required to maintain small intestinal stem cell populations - RNA-sequencing

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Project description:The purpose of this study was to characterise iPSC-derived human intestinal epithelial organoids (iPSCo) by comparing these cultures with primary purified intestinal epithelial cells (IEC). Intestinal epithelial organoid (IEO) cultures were derived from at least three different lines of iPSCs, RNA was extracted and gene expression was profiled using RNA-sequencing. We compared these profiles with datasets we have previously derived from purified IEC from mature terminal ileum (TI) and sigmoid colon (SC) as well as human fetal proximal gut (FPG) and fetal distal gut (FDG).

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