Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of <i>Hnrnp I</i> Knockout Mice
(1) Background: Knockout (KO) of heterogeneous nuclear ribonucleoprotein I (<i>Hnrnp I</i>) in mouse intestinal epithelial cells (IECs) induced a severe inflammatory response in the colon, followed by hyperproliferation. This study aimed to investigate the epithelial lineage dynamics and...
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MDPI AG
2023-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/10/2734 |
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| author | Guanying (Bianca) Xu Yuan-Xiang Pan Wenyan Mei Hong Chen |
| author_facet | Guanying (Bianca) Xu Yuan-Xiang Pan Wenyan Mei Hong Chen |
| author_sort | Guanying (Bianca) Xu |
| collection | DOAJ |
| description | (1) Background: Knockout (KO) of heterogeneous nuclear ribonucleoprotein I (<i>Hnrnp I</i>) in mouse intestinal epithelial cells (IECs) induced a severe inflammatory response in the colon, followed by hyperproliferation. This study aimed to investigate the epithelial lineage dynamics and cell–cell communications that underlie inflammation and colitis. (2) Methods: Single cells were isolated from the colons of wildtype (WT) and KO mice and used in scRNA-seq. Whole colons were collected for immunofluorescence staining and cytokine assays. (3) Results: from scRNA-seq, the number of DCLK1 + colonic tuft cells was significantly higher in the <i>Hnrnp I</i> KO mice compared to the WT mice. This was confirmed by immunofluorescent staining of DCLK1. The DCLK1 + colonic tuft cells in KO mice developed unique communications with lymphocytes via interactions between surface L1 cell adhesion molecule (L1CAM) and integrins. In the KO mice colons, a significantly elevated level of inflammatory cytokines IL4, IL6, and IL13 were observed, which marks type-2 immune responses directed by group 2 innate lymphoid cells (ILC2s). (4) Conclusions: This study demonstrates one critical cellular function of colonic tuft cells, which facilitates type-2 immune responses by communicating with ILC2s via the L1CAM–integrins interaction. This communication promotes pro-inflammatory signaling pathways in ILC2, leading to the increased secretion of inflammatory cytokines. |
| first_indexed | 2024-03-10T21:25:35Z |
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| id | doaj.art-8c9ba446d9cf48709e92bca170fb1cc0 |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T21:25:35Z |
| publishDate | 2023-10-01 |
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| spelling | doaj.art-8c9ba446d9cf48709e92bca170fb1cc02023-11-19T15:46:19ZengMDPI AGBiomedicines2227-90592023-10-011110273410.3390/biomedicines11102734Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of <i>Hnrnp I</i> Knockout MiceGuanying (Bianca) Xu0Yuan-Xiang Pan1Wenyan Mei2Hong Chen3Department of Food Science and Human Nutrition, College of Agricultural, Consumer, and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Food Science and Human Nutrition, College of Agricultural, Consumer, and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADivision of Nutritional Sciences, College of Agricultural, Consumer, and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Food Science and Human Nutrition, College of Agricultural, Consumer, and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA(1) Background: Knockout (KO) of heterogeneous nuclear ribonucleoprotein I (<i>Hnrnp I</i>) in mouse intestinal epithelial cells (IECs) induced a severe inflammatory response in the colon, followed by hyperproliferation. This study aimed to investigate the epithelial lineage dynamics and cell–cell communications that underlie inflammation and colitis. (2) Methods: Single cells were isolated from the colons of wildtype (WT) and KO mice and used in scRNA-seq. Whole colons were collected for immunofluorescence staining and cytokine assays. (3) Results: from scRNA-seq, the number of DCLK1 + colonic tuft cells was significantly higher in the <i>Hnrnp I</i> KO mice compared to the WT mice. This was confirmed by immunofluorescent staining of DCLK1. The DCLK1 + colonic tuft cells in KO mice developed unique communications with lymphocytes via interactions between surface L1 cell adhesion molecule (L1CAM) and integrins. In the KO mice colons, a significantly elevated level of inflammatory cytokines IL4, IL6, and IL13 were observed, which marks type-2 immune responses directed by group 2 innate lymphoid cells (ILC2s). (4) Conclusions: This study demonstrates one critical cellular function of colonic tuft cells, which facilitates type-2 immune responses by communicating with ILC2s via the L1CAM–integrins interaction. This communication promotes pro-inflammatory signaling pathways in ILC2, leading to the increased secretion of inflammatory cytokines.https://www.mdpi.com/2227-9059/11/10/2734tuftILCsL1CAMcoloninflammationcolitis |
| spellingShingle | Guanying (Bianca) Xu Yuan-Xiang Pan Wenyan Mei Hong Chen Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of <i>Hnrnp I</i> Knockout Mice Biomedicines tuft ILCs L1CAM colon inflammation colitis |
| title | Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of <i>Hnrnp I</i> Knockout Mice |
| title_full | Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of <i>Hnrnp I</i> Knockout Mice |
| title_fullStr | Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of <i>Hnrnp I</i> Knockout Mice |
| title_full_unstemmed | Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of <i>Hnrnp I</i> Knockout Mice |
| title_short | Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of <i>Hnrnp I</i> Knockout Mice |
| title_sort | single cell rna sequencing scrna seq identifies l1cam as a key mediator between epithelial tuft cell and innate lymphoid cell in the colon of i hnrnp i i knockout mice |
| topic | tuft ILCs L1CAM colon inflammation colitis |
| url | https://www.mdpi.com/2227-9059/11/10/2734 |
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