A stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell niche
Abstract Background The nutrient-absorbing villi of small intestines are renewed and repaired by intestinal stem cells (ISCs), which reside in a well-organized crypt structure. Genetic studies have shown that Wnt molecules secreted by telocytes, Gli1 + stromal cells, and epithelial cells are require...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-023-01667-2 |
| _version_ | 1827633164528386048 |
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| author | Jinnan Xiang Jigang Guo Shaoyang Zhang Hongguang Wu Ye-Guang Chen Junping Wang Baojie Li Huijuan Liu |
| author_facet | Jinnan Xiang Jigang Guo Shaoyang Zhang Hongguang Wu Ye-Guang Chen Junping Wang Baojie Li Huijuan Liu |
| author_sort | Jinnan Xiang |
| collection | DOAJ |
| description | Abstract Background The nutrient-absorbing villi of small intestines are renewed and repaired by intestinal stem cells (ISCs), which reside in a well-organized crypt structure. Genetic studies have shown that Wnt molecules secreted by telocytes, Gli1 + stromal cells, and epithelial cells are required for ISC proliferation and villus homeostasis. Intestinal stromal cells are heterogeneous and single-cell profiling has divided them into telocytes/subepithelial myofibroblasts, myocytes, pericytes, trophocytes, and Pdgfra low stromal cells. Yet, the niche function of these stromal populations remains incompletely understood. Results We show here that a Twist2 stromal lineage, which constitutes the Pdgfra low stromal cell and trophocyte subpopulations, maintains the crypt structure to provide an inflammation-restricting niche for regenerating ISCs. Ablating Twist2 lineage cells or deletion of one Wntless allele in these cells disturbs the crypt structure and impairs villus homeostasis. Upon radiation, Wntless haplo-deficiency caused decreased production of anti-microbial peptides and increased inflammation, leading to defective ISC proliferation and crypt regeneration, which were partially rescued by eradication of commensal bacteria. In addition, we show that Wnts secreted by Acta2 + subpopulations also play a role in crypt regeneration but not homeostasis. Conclusions These findings suggest that ISCs may require different niches for villus homeostasis and regeneration and that the Twist2 lineage cells may help to maintain a microbe-restricted environment to allow ISC-mediated crypt regeneration. |
| first_indexed | 2024-03-09T14:55:43Z |
| format | Article |
| id | doaj.art-f6f8689f796447e3bb47d4a24365f0aa |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-03-09T14:55:43Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-f6f8689f796447e3bb47d4a24365f0aa2023-11-26T14:14:32ZengBMCBMC Biology1741-70072023-08-0121111510.1186/s12915-023-01667-2A stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell nicheJinnan Xiang0Jigang Guo1Shaoyang Zhang2Hongguang Wu3Ye-Guang Chen4Junping Wang5Baojie Li6Huijuan Liu7The Bio-X Institutes, Shanghai Jiao Tong UniversityThe Bio-X Institutes, Shanghai Jiao Tong UniversityThe Bio-X Institutes, Shanghai Jiao Tong UniversityThe Bio-X Institutes, Shanghai Jiao Tong UniversityState Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua UniversityChongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityThe Bio-X Institutes, Shanghai Jiao Tong UniversityThe Bio-X Institutes, Shanghai Jiao Tong UniversityAbstract Background The nutrient-absorbing villi of small intestines are renewed and repaired by intestinal stem cells (ISCs), which reside in a well-organized crypt structure. Genetic studies have shown that Wnt molecules secreted by telocytes, Gli1 + stromal cells, and epithelial cells are required for ISC proliferation and villus homeostasis. Intestinal stromal cells are heterogeneous and single-cell profiling has divided them into telocytes/subepithelial myofibroblasts, myocytes, pericytes, trophocytes, and Pdgfra low stromal cells. Yet, the niche function of these stromal populations remains incompletely understood. Results We show here that a Twist2 stromal lineage, which constitutes the Pdgfra low stromal cell and trophocyte subpopulations, maintains the crypt structure to provide an inflammation-restricting niche for regenerating ISCs. Ablating Twist2 lineage cells or deletion of one Wntless allele in these cells disturbs the crypt structure and impairs villus homeostasis. Upon radiation, Wntless haplo-deficiency caused decreased production of anti-microbial peptides and increased inflammation, leading to defective ISC proliferation and crypt regeneration, which were partially rescued by eradication of commensal bacteria. In addition, we show that Wnts secreted by Acta2 + subpopulations also play a role in crypt regeneration but not homeostasis. Conclusions These findings suggest that ISCs may require different niches for villus homeostasis and regeneration and that the Twist2 lineage cells may help to maintain a microbe-restricted environment to allow ISC-mediated crypt regeneration.https://doi.org/10.1186/s12915-023-01667-2MesenchymalNicheISCWntlessPaneth cellInflammation |
| spellingShingle | Jinnan Xiang Jigang Guo Shaoyang Zhang Hongguang Wu Ye-Guang Chen Junping Wang Baojie Li Huijuan Liu A stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell niche BMC Biology Mesenchymal Niche ISC Wntless Paneth cell Inflammation |
| title | A stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell niche |
| title_full | A stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell niche |
| title_fullStr | A stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell niche |
| title_full_unstemmed | A stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell niche |
| title_short | A stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell niche |
| title_sort | stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell niche |
| topic | Mesenchymal Niche ISC Wntless Paneth cell Inflammation |
| url | https://doi.org/10.1186/s12915-023-01667-2 |
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