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Spatial gene expression maps of the intestinal lymphoid follicle and associated epithelium identify zonated expression programs

ABSTRACT: Spatial gene expression maps of the intestinal lymphoid follicle and associated epithelium identify zonated expression programs

PROVIDER: PRJNA707544 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13892502_1.fastq.gz	Fastqsanger.gz
	SRR13892502_2.fastq.gz	Fastqsanger.gz
	SRR13892503_1.fastq.gz	Fastqsanger.gz
	SRR13892503_2.fastq.gz	Fastqsanger.gz
	SRR13892504_1.fastq.gz	Fastqsanger.gz

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Spatial gene expression maps of the intestinal lymphoid follicle and associated epithelium identify zonated expression programs.

Project description:The intestine is lined with isolated lymphoid follicles (ILFs) that facilitate sampling of luminal antigens to elicit immune responses. Technical challenges related to the scarcity and small sizes of ILFs and their follicle-associated epithelium (FAE) impeded the characterization of their spatial gene expression programs. Here, we combined RNA sequencing of laser capture microdissected tissues with single-molecule transcript imaging to obtain a spatial gene expression map of the ILF and its associated FAE in the mouse small intestine. We identified zonated expression programs in both follicles and FAEs, with a decrease in enterocyte antimicrobial and absorption programs and a partial induction of expression programs normally observed at the villus tip. We further identified Lepr+ subepithelial telocytes at the FAE top, which are distinct from villus tip Lgr5+ telocytes. Our analysis exposes the epithelial and mesenchymal cell states associated with ILFs.

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Spatial gene expression maps of the intestinal lymphoid follicle and associated epithelium identify zonated expression programs

Project description:We combined RNA sequencing of laser capture microdissected-tissues with single molecule transcript imaging to obtain a spatial gene expression map of the ILF and its associated FAE in the mouse small intestine.

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Project description:To investigate the underlying molecular principles of metabolic and morphogenic zonation of the human liver lobule, we generated an integrated epigenetic map across three zones (pericentral, intermediate and periportal) by methylation and transcriptomic analysis of hepatocytes captured by laser micro-dissection. We observe a deep link between epigenetic zonation of human liver and a zonated expression of metabolic and morphogenic pathways: Key transcriptionally zonated enzymes in xenobiotic and glutamine metabolism show a strong anticorrelated methylation gradient indicating that zonal expression of these genes is partly controlled by epigenetic programs. Zonated DNA-methylation at binding sites of uniformly expressed transcription factors such as HNF4A and RXRα points to an epigenetic layer in regulatory networks and a zonated activity of their nuclear ligands and drugs such as fibrates and bile acids. The same holds for genes of the wnt morphogen pathway whose expression show a zonated methylation at binding sites of TCF4L2. A strong pericentral expression of LGR5 and AXIN2 and a corresponding expression gradient of the liver progenitor marker TBX3, indicates a predominant pericentral source of hepatocyte regeneration under steady-state conditions in humans. Conversely, the periportal expression of NOTCH and EPCAM at the border to the biliary tree as source of regeneration under injury conditions. Overall our data provide a deep understanding of molecular control of the zonal organisation in the human liver.

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Distinct microRNA expression profiles in follicle-associated epithelium and villous epithelium.

Project description:M cells in follicle-associated epithelium (FAE) covering intestinal lymphoid follicles serve as a portal of entry for particulate antigens (Kanaya and Ohno, 2014 [1]). Despite their biological significance, molecular mechanisms that govern M-cell differentiation and function have not been fully elucidated. MicroRNAs (miRNAs) have a role to control host gene expression profiles that modulate cellular physiology and characteristic. Many studies have shown that miRNAs regulate diverse biological processes including developmental timing, differentiation and growth control of cells and tissues (Ivey and Srivastava, 2010 [2]). miRNAs are also relevant to differentiation and function of intestinal epithelium (McKenna et al., 2010 [3]; Runtsch et al., 2014 [4]). Expression profiles and functions of miRNAs in the intestinal epithelium have been examined in jejunal and colonic mucosa [3]. In contrast, those in FAE remain uncharacterized. To address this deficiency, we isolated Peyer's Patch (PP) FAE and villous epithelium (VE) surrounding the FAE, and compared the miRNA expression profiles of FAE and VE by microarray analysis. This revealed that 43 miRNAs were up-regulated, whereas 9 miRNAs were down-regulated, in FAE compared to VE. A unique pattern of miRNA expression by FAE may reflect important diversity in cellular phenotypes and/or functional features of FAE. All microarray data has been deposited at GEO under accession number GSE46264.

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2011-09-02 | E-GEOD-31239 | biostudies-arrayexpress

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