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Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell [scATAC-Seq]

ABSTRACT: Enterocytes and four classic secretory cell types derive from intestinal epithelial stem cells. Based on morphology, location, and canonical markers, goblet and Paneth cells are considered distinct secretory types. Here, we report high overlap in their transcripts and sites of accessible chromatin, in marked contrast to those of their enteroendocrine or tuft cell siblings. Mouse and human goblet and Paneth cells express extraordinary fractions of few antimicrobial genes, which reflect specific responses to local niches. Wnt signaling retains some ATOH1+ secretory cells in crypt bottoms, where absence of BMP signaling potently induces Paneth features. Cells that migrate away from crypt bottoms encounter BMPs and thereby acquire goblet properties. These phenotypes and underlying accessible cis-elements interconvert in post-mitotic cells. Thus, goblet and Paneth properties represent alternative phenotypic manifestations of a common signal-responsive terminal cell type. These findings reveal exquisite niche-dependent cell plasticity and cis-regulatory dynamics in likely response to antimicrobial needs

ORGANISM(S): Mus musculus

PROVIDER: GSE271615 | GEO | 2025/04/08

REPOSITORIES: GEO

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Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell [scRNA-Seq]

Project description:Enterocytes and four classic secretory cell types derive from intestinal epithelial stem cells. Based on morphology, location, and canonical markers, goblet and Paneth cells are considered distinct secretory types. Here, we report high overlap in their transcripts and sites of accessible chromatin, in marked contrast to those of their enteroendocrine or tuft cell siblings. Mouse and human goblet and Paneth cells express extraordinary fractions of few antimicrobial genes, which reflect specific responses to local niches. Wnt signaling retains some ATOH1+ secretory cells in crypt bottoms, where absence of BMP signaling potently induces Paneth features. Cells that migrate away from crypt bottoms encounter BMPs and thereby acquire goblet properties. These phenotypes and underlying accessible cis-elements interconvert in post-mitotic cells. Thus, goblet and Paneth properties represent alternative phenotypic manifestations of a common signal-responsive terminal cell type. These findings reveal exquisite niche-dependent cell plasticity and cis-regulatory dynamics in likely response to antimicrobial needs.

2025-04-08 | GSE271614 | GEO

Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell [ATAC-Seq]

2025-04-08 | GSE271613 | GEO

Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell [RNA-Seq]

2025-04-08 | GSE271611 | GEO

Reg4+ Deep Crypt Secretory cells function as epithelial niche for Lgr5+ stem cells in colon

Project description:Lgr5+ stem cells reside at crypt bottoms of the small and large intestine. Small intestinal Paneth cells supply Wnt3, EGF and Notch signals to neighboring Lgr5+ stem cells. While the colon lacks Paneth cells, Deep Crypt Secretory (DCS) cells are intermingled with Lgr5+ stem cells at crypt bottoms. Here, we report Reg4 as a marker of DCS cells. To investigate a niche function, we eliminated DCS cells using the diphtheria-toxin receptor gene knocked into the murine Reg4 locus. Ablation of DCS cells results in loss of stem cells from colonic crypts and disrupts gut homeostasis and colon mini-gut formation. In agreement, sorted Reg4+ DCS cells promote organoid formation of single Lgr5+ colon stem cells. Stem cells are forced to generate DCS cells in vitro by combined Notch inhibition and Wnt activation. We conclude that Reg4+ DCS cells serve as Paneth cell equivalents in the colon crypt niche.

2016-10-05 | GSE63256 | GEO

Expression data from mouse crypt

Project description:Paneth cells originate in the stem cell region near the bottom of the gland and release a large number of secretory granules containing antimicrobials. The antimicrobial-rich granules are discharged into the crypt lumen and prevent microbial invasion of the crypt and defend the gland stem cells from microbial damage. We examined the global gene expression profiles in crypt IECs using the Clariom S sDNA array. We analyzed mRNA panels of antimicrobial peptides (AMPs) produced in CSN8ΔIEC and CSN8fl/fl mice.

2018-09-03 | GSE108132 | GEO

Single-cell RNA-seq reveals distinct maturation stages of the Paneth cell lineage

Project description:Paneth cells (PCs) are long-lived secretory cells that reside at the bottoms of small intestinal crypts. Besides serving as niche cells for the neighboring Lgr5-positive stem cells, PCs secrete granules containing a broad spectrum of antimicrobial proteins, including lysozymes and defensins1. Here, we have used single-cell RNA sequencing to explore PC differentiation. We found a maturation gradient from early secretory progenitors to mature PCs, capturing the full maturation path of PCs. Moreover, differential expression of a subset of defensin genes in lysozyme-high PCs, e.g. Defa20, reveals at least two distinct stages of maturation. We traced Lgr5+ stem cells from Lgr5-CreERT2 C57Bl6/J mice bred to a Rosa26LSL-YFP reporter mice and sorted YFP+ cells 5 days, 3 weeks and 8 weeks after tamoxifen injection.

2016-06-23 | E-GEOD-76408 | biostudies-arrayexpress

Single-cell RNA-seq reveals distinct maturation stages of the Paneth cell lineage

2016-06-23 | GSE76408 | GEO

Proteomic profiling of mouse Paneth cells microdissected from small intestinal tissue

Project description:Paneth cells are antimicrobial peptide-secreting cells located at the base of the crypts of the small intestine. The proteome of Paneth cells is not well defined because of their co-existence with stem cells making it difficult to culture Panth cells alone in vitro. Using a simplied toluidine blue O method for staining mouse intestinal tissue, laser capture microdissection (LCM) to isolate cells from the crypt region and surfactant assisted one pot protein digestion, we identified more than 1,300 proteins from crypts equivalent to 18,000 cells. Compared with the proteomes of villi and smooth muscle regions, the crypt proteome is highly enriched in defensins, lysozymes and other antimicrobial peptides that are characteristic of Paneth cells. The sensitivity of the LCM-based proteomics approach was also assessed using a smaller number of cell equivalent tissues, a comparable proteomic coverage can be achieved with 3,600 cells. This work is the first proteomics study of intestinal tissue enriched with Paneth cells. The simplied workflow enables profiling of Paneth cell associated pathological changes at the proteome level directly from frozen intestinal tissue. It may also be useful for proteomics studies of other spatially resolved cell types from other tissues.

2022-10-12 | PXD034143 | Pride

The Ets domain transcription factor Spdef drives maturation of Goblet and Paneth cells in the intestinal epithelium

Project description:BACKGROUND & AIMS: Stems cells within the intestinal epithelium generate daughter cells which undergo lineage commitment and maturation through the concerted action of the Wnt and Notch signalling cascades. Both pathways, in turn, regulate transcription factor networks which further define differentiation towards either enterocytes or one of three secretory cell lineages (Paneth, goblet or enteroendocrine cells). In this manuscript, we identified the Ets domain transcription factor, Spdef, as a novel lineage maker of goblet and Paneth cells. METHODS: To address the function of Spdef in vivo, we inactivated the Spdef gene and analysed the intestinal phenotype using a range of histological techniques and DNA microarray profiling. RESULTS: In accordance with the expression data we found that loss of Spdef severely impaired the maturation of goblet and Paneth cells and conversely lead to an accumulation of immature secretory progenitors. Moreover, we provide evidence suggesting that Spdef positively and negatively regulates a specific subset of goblet and Paneth cell genes including Cryptdins, Mmp7, Ang4, Kallikreins, and Muc2. CONCLUSION: We propose a model whereby Spdef acts downstream of Math1 to promote terminal differentiation of a secretory progenitor pool towards Paneth and goblet cells. Keywords: expression profiling

2010-02-10 | GSE14892 | GEO

Engineered glycocalix regulates stem cell proliferation in murine crypt organoids

Project description:At the base of the intestinal crypt, long-lived Lgr5+ stem cells are intercalated by Paneth cells that provide essential niche signals for stem-cell maintenance. This unique epithelial anatomy makes the intestinal crypt one of the most accessible models for the study of adult stem cell biology. The glycosylation patterns of this compartment are poorly characterized and the impact of glycans on stem cell differentiation remains largely unexplored. We found that Paneth cells, but not Lgr5+ stem cells, express abundant terminal N-acetyllactosamine (LacNAc). Employing an enzymatic method to edit glycans in cultured crypt organoids, we assessed the functional role of LacNAc in the intestinal crypt. We show that blocking access to LacNAc on Paneth cells leads to hyperproliferation of the neighbouring Lgr5+ stem cells, which is accompanied by the down-regulation of genes that are known as negative regulators of proliferation

2017-12-27 | GSE108512 | GEO

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