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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.

2024-07-01 | GSE270546 | GEO

Epigenetic reprogramming of intestinal stemness by dietary arachidonic acid [Organoid]

Project description:Single cell transcriptomic profiling (sc RNA-seq) of arachidonic acid (AA) induced gene expression pogram associated with regeneration in intestinal organoids.

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Epigenetic reprogramming of intestinal stemness by dietary arachidonic acid [In_vivo]

Project description:Single cell transcriptomic profiling (sc RNA-seq) of diatery arachidonic acid (AA) induced gene expression pogram associated with regeneration in intestinal organoids.

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Transcriptome profiling of Drosophila Wild Type and Sc overexpressed intestinal progenitor cells

Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare transcriptome profiling (RNA-seq) of intestinal progenitor cells in Drosophila wild type and Sc overexpressed midgut. Methods: mRNA profiles of intestinal progenitor cells isolated from 2-day-old wild-type (Ctrl) and Sc overexpressed(ScOE) Drosophila midgut were generated by deep sequencing using Illumina HiSeq 4000. Results:

2018-02-02 | GSE102569 | GEO

Setdb1 in required for intestinal epithelial differentiation and the prevention of intestinal inflammation

Project description:The intestinal epithelium is a complex, constitutively renewing tissue composed of functionally distinct intestinal epithelial cells (IECs), whose specific cell fates are established and maintained through cell-specific activity of transcription factors, as well as precise gene silencing by chromatin compaction. By facilitating chromatin condensation through histone modification, SETDB1, a histone-lysine N-methyltransferase, is one of the central factors involved in regulation of epigenetic transcriptional repression. Therefore, we set out to study the potential roles of SETDB1 in intestinal epithelial homeostasis and inflammatory bowel disease (IBD). We used RNA-sequencing to profile gene expression changes in intestinal epithelial cells of mice with tamoxifen (TAM)-inducible (Villin-CreERT2) IEC-specific deletion of Setdb1 on day 2 post TAM-injection start, compared to TAM-treated wild-type littermates. We find an expression profile which indicates intestinal epithelial cell death and induction of type I interferon signaling, as a result of de-repression of endogenous retroviruses.

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Gene expression in intestinal epithelial crypt and villus cell populations

Project description:We analyzed gene expression profiles in isolated mouse LGR5+ intestinal stem cells, lineage-specific enterocyte and secretory progenitors, and terminally differentiated villus enterocytes. Gene Ontology analyses of cell type-specific transcripts indicated their expected biological functions. We hybridized Affmetrix 430A 2.0 mouse microarrays with processed RNA isolated from purified Lgr5+ intestinal stem cells, secretory (Sec-Pro) and enterocyte (Ent-Pro) crypt progenitors, and mature villus enterocytes (ENT).

2014-01-06 | E-GEOD-51398 | biostudies-arrayexpress

KAT2A and KAT2B prevents double-stranded RNA formation and interferon signaling to maintain intestinal stem cell renewal

Project description:Histone acetyltransferases KAT2A and KAT2B are paralogs highly expressed in the intestinal epithelium, but their functions are not well understood. In this study, double knockout of murine Kat2 genes in the intestinal epithelium was lethal, resulting in diminished H3K9ac expression, loss of stem cells, and robust activation of interferon signaling. Use of pharmacological agents and sterile organoid cultures indicated a cell-intrinsic double-stranded RNA trigger for interferon signaling. Acetyl-proteomics and dsRIP-seq were employed to interrogate the mechanism behind this response, which identified self-derived, mitochondria- encoded double-stranded RNA as the source of intrinsic interferon signaling. KAT2A and KAT2B therefore play an essential role in regulating mitochondrial functions as well as maintaining intestinal health.

2023-07-07 | MSV000092370 | MassIVE

Distinct mesenchymal cell populations generate the essential intestinal BMP signaling gradient

Project description:The intestinal epithelium requires trophic factors and signaling gradients to maintain proper positioning of Intestinal Stem Cells (ISC) and proper differentiation of ISCs. Because the underlying mesenchyme is composed of numerous cell types, we utilized both transgenic and antibody methods to isolate specific mesenchymal populations including GFP-hi and GFP-lo cells from the murine transgenic PDGFRAH2BEGFP mouse (Jackson, #007669), endothelial and lymphatic endothelial cells via antibody for CD31+LYVE1- and CD31+LYVE1+, respectively. We found distinct molecular signatures of these cell types and focused our analyses on known trophic factors of the overlaying intestinal epithelium.

2020-01-17 | GSE130681 | GEO

Bulk cell RNAseq of putatative intestinal stem cell populations

Project description:A comparative bulk cell RNA-seq analysis of diverse intestinal stem cell populations was performed, for cells expressing the following markers: Lgr5-eGFPhi, Cd166+, Cd24lo, Grp78, upper side population (SP), Bmi1, mTert, Hopx, Dclk1, a lower side population (SP)

2017-07-10 | GSE99815 | GEO

RNA-sequencing of human induced pluripotent stem cell-derived intestinal epithelial organoids

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).

2018-10-22 | E-MTAB-7306 | biostudies-arrayexpress

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