Intestinal stromal cell types in health and inflammatory bowel disease uncovered by single-cell transcriptomics
<p>Colonic stromal cells provide critical structural support but also regulate immunity, tolerance and inflammatory responses in the mucosa. Substantial variability and plasticity of mucosal stromal cells has been reported but a paucity of distinct marker genes exist to identify distinct cell...
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| Format: | Thesis |
| Language: | English |
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2017
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| _version_ | 1817932136527691776 |
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| author | Kinchen, J |
| author2 | Simmons, A |
| author_facet | Simmons, A Kinchen, J |
| author_sort | Kinchen, J |
| collection | OXFORD |
| description | <p>Colonic stromal cells provide critical structural support but also regulate immunity, tolerance and inflammatory responses in the mucosa. Substantial variability and plasticity of mucosal stromal cells has been reported but a paucity of distinct marker genes exist to identify distinct cell states. Here single-cell RNA-sequencing is used to document heterogeneity and subtype specific markers of individual colonic stromal cells in human and mouse.</p> <p>Marker-free transcriptional clustering of fibroblast-like cells derived from healthy human tissue reveals distinct populations corresponding to myofibroblasts and three transcriptionally and functionally dissimilar populations of fibroblasts. A <em>SOX6</em> high fibroblast subset occupies a position adjacent to the epithelial basement membrane and expresses multiple epithelial morphogens including WNT5A and BMP2. Additional fibroblast subtypes show specific enrichment for chemokine signalling and prostaglandin E<sub>2</sub> synthesis respectively.</p> <p>In ulcerative colitis, substantial remodelling occurs with depletion of the SOX6 high population and emergence of an immune enriched population expressing genes associated with fibroblastic reticular cells including <em>CCL19, CCL21</em> and <em>IL33</em>.</p> <p>A large murine dataset comprising over 7,000 colonic mesenchymal cells from an acute colitis model and matched healthy controls reveals strong preservation of the <em>SOX6</em> high and myofibroblast transcriptional signatures. Unsupervised pseudotemporal ordering is used to relate fibroblast subsets to one another producing a branched developmental hierarchy that includes a potential progenitor population with mesothelial characteristics at its origin. This work provides a molecular basis for re-classification of colonic stromal cells and identifies pathological changes in these cells underpinning inflammation in UC.</p> |
| first_indexed | 2024-03-06T19:26:42Z |
| format | Thesis |
| id | oxford-uuid:1bf9d8f0-6d09-46f5-9d1e-3c9e0b826618 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:33:07Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | oxford-uuid:1bf9d8f0-6d09-46f5-9d1e-3c9e0b8266182024-12-01T16:17:20ZIntestinal stromal cell types in health and inflammatory bowel disease uncovered by single-cell transcriptomicsThesishttp://purl.org/coar/resource_type/c_db06uuid:1bf9d8f0-6d09-46f5-9d1e-3c9e0b826618Inflammatory bowel diseasesMesenchymal stem cells--DifferentiationEnglishORA Deposit2017Kinchen, JSimmons, A<p>Colonic stromal cells provide critical structural support but also regulate immunity, tolerance and inflammatory responses in the mucosa. Substantial variability and plasticity of mucosal stromal cells has been reported but a paucity of distinct marker genes exist to identify distinct cell states. Here single-cell RNA-sequencing is used to document heterogeneity and subtype specific markers of individual colonic stromal cells in human and mouse.</p> <p>Marker-free transcriptional clustering of fibroblast-like cells derived from healthy human tissue reveals distinct populations corresponding to myofibroblasts and three transcriptionally and functionally dissimilar populations of fibroblasts. A <em>SOX6</em> high fibroblast subset occupies a position adjacent to the epithelial basement membrane and expresses multiple epithelial morphogens including WNT5A and BMP2. Additional fibroblast subtypes show specific enrichment for chemokine signalling and prostaglandin E<sub>2</sub> synthesis respectively.</p> <p>In ulcerative colitis, substantial remodelling occurs with depletion of the SOX6 high population and emergence of an immune enriched population expressing genes associated with fibroblastic reticular cells including <em>CCL19, CCL21</em> and <em>IL33</em>.</p> <p>A large murine dataset comprising over 7,000 colonic mesenchymal cells from an acute colitis model and matched healthy controls reveals strong preservation of the <em>SOX6</em> high and myofibroblast transcriptional signatures. Unsupervised pseudotemporal ordering is used to relate fibroblast subsets to one another producing a branched developmental hierarchy that includes a potential progenitor population with mesothelial characteristics at its origin. This work provides a molecular basis for re-classification of colonic stromal cells and identifies pathological changes in these cells underpinning inflammation in UC.</p> |
| spellingShingle | Inflammatory bowel diseases Mesenchymal stem cells--Differentiation Kinchen, J Intestinal stromal cell types in health and inflammatory bowel disease uncovered by single-cell transcriptomics |
| title | Intestinal stromal cell types in health and inflammatory bowel disease uncovered by single-cell transcriptomics |
| title_full | Intestinal stromal cell types in health and inflammatory bowel disease uncovered by single-cell transcriptomics |
| title_fullStr | Intestinal stromal cell types in health and inflammatory bowel disease uncovered by single-cell transcriptomics |
| title_full_unstemmed | Intestinal stromal cell types in health and inflammatory bowel disease uncovered by single-cell transcriptomics |
| title_short | Intestinal stromal cell types in health and inflammatory bowel disease uncovered by single-cell transcriptomics |
| title_sort | intestinal stromal cell types in health and inflammatory bowel disease uncovered by single cell transcriptomics |
| topic | Inflammatory bowel diseases Mesenchymal stem cells--Differentiation |
| work_keys_str_mv | AT kinchenj intestinalstromalcelltypesinhealthandinflammatoryboweldiseaseuncoveredbysinglecelltranscriptomics |