EGF and BMPs govern differentiation and patterning in human gastric glands
Background & Aims The homeostasis of the gastrointestinal epithelium relies on cell regeneration and differentiation into distinct lineages organised inside glands and crypts. Regeneration depends on WNT/β-Catenin pathway activation, but to understand homeostasis and its dysregulation in disease...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2021
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| _version_ | 1797069395355238400 |
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| author | Wölffling, S Daddi, AA Imai-Matsushima, A Fritsche, K Goosmann, C Traulsen, J Lisle, R Schmid, M del Mar Reines-Benassar, M Pfannkuch, L Brinkmann, V Bornschein, J Peter Malfertheiner Ordemann, J Link, A Meyer, TF Boccellato, F |
| author_facet | Wölffling, S Daddi, AA Imai-Matsushima, A Fritsche, K Goosmann, C Traulsen, J Lisle, R Schmid, M del Mar Reines-Benassar, M Pfannkuch, L Brinkmann, V Bornschein, J Peter Malfertheiner Ordemann, J Link, A Meyer, TF Boccellato, F |
| author_sort | Wölffling, S |
| collection | OXFORD |
| description | Background & Aims
The homeostasis of the gastrointestinal epithelium relies on cell regeneration and differentiation into distinct lineages organised inside glands and crypts. Regeneration depends on WNT/β-Catenin pathway activation, but to understand homeostasis and its dysregulation in disease we need to identify the signalling microenvironment governing cell differentiation. By using gastric glands as a model, we have identified the signals inducing differentiation of surface mucus-, zymogen- and gastric acid- producing cells.
Methods
We generated mucosoid cultures from the human stomach and exposed them to different growth factors to obtain cells with features of differentiated foveolar, chief and parietal cells. We localised the source of the growth factors in the tissue of origin.
Results
We show that EGF is the major fate determinant distinguishing the surface and inner part of human gastric glands. In combination with BMP/NOGGIN signals, EGF controls the differentiation of foveolar cells vs. parietal or chief cells. We also show that EGF is likely to underlie alteration of the gastric mucosa in the pre-cancerous condition atrophic gastritis.
Conclusions
Use of our recently established mucosoid cultures in combination with analysis of the tissue-of-origin provided a robust strategy to understand differentiation and patterning of human tissue and allowed us to draw a new, detailed map of the signalling microenvironment in the human gastric glands.
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| first_indexed | 2024-03-06T22:23:48Z |
| format | Journal article |
| id | oxford-uuid:55f70967-8857-4066-80e8-0665b6ed8490 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:23:48Z |
| publishDate | 2021 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:55f70967-8857-4066-80e8-0665b6ed84902022-03-26T16:47:28ZEGF and BMPs govern differentiation and patterning in human gastric glandsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:55f70967-8857-4066-80e8-0665b6ed8490EnglishSymplectic ElementsElsevier2021Wölffling, SDaddi, AAImai-Matsushima, AFritsche, KGoosmann, CTraulsen, JLisle, RSchmid, Mdel Mar Reines-Benassar, MPfannkuch, LBrinkmann, VBornschein, JPeter MalfertheinerOrdemann, JLink, AMeyer, TFBoccellato, FBackground & Aims The homeostasis of the gastrointestinal epithelium relies on cell regeneration and differentiation into distinct lineages organised inside glands and crypts. Regeneration depends on WNT/β-Catenin pathway activation, but to understand homeostasis and its dysregulation in disease we need to identify the signalling microenvironment governing cell differentiation. By using gastric glands as a model, we have identified the signals inducing differentiation of surface mucus-, zymogen- and gastric acid- producing cells. Methods We generated mucosoid cultures from the human stomach and exposed them to different growth factors to obtain cells with features of differentiated foveolar, chief and parietal cells. We localised the source of the growth factors in the tissue of origin. Results We show that EGF is the major fate determinant distinguishing the surface and inner part of human gastric glands. In combination with BMP/NOGGIN signals, EGF controls the differentiation of foveolar cells vs. parietal or chief cells. We also show that EGF is likely to underlie alteration of the gastric mucosa in the pre-cancerous condition atrophic gastritis. Conclusions Use of our recently established mucosoid cultures in combination with analysis of the tissue-of-origin provided a robust strategy to understand differentiation and patterning of human tissue and allowed us to draw a new, detailed map of the signalling microenvironment in the human gastric glands. |
| spellingShingle | Wölffling, S Daddi, AA Imai-Matsushima, A Fritsche, K Goosmann, C Traulsen, J Lisle, R Schmid, M del Mar Reines-Benassar, M Pfannkuch, L Brinkmann, V Bornschein, J Peter Malfertheiner Ordemann, J Link, A Meyer, TF Boccellato, F EGF and BMPs govern differentiation and patterning in human gastric glands |
| title | EGF and BMPs govern differentiation and patterning in human gastric glands |
| title_full | EGF and BMPs govern differentiation and patterning in human gastric glands |
| title_fullStr | EGF and BMPs govern differentiation and patterning in human gastric glands |
| title_full_unstemmed | EGF and BMPs govern differentiation and patterning in human gastric glands |
| title_short | EGF and BMPs govern differentiation and patterning in human gastric glands |
| title_sort | egf and bmps govern differentiation and patterning in human gastric glands |
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