Sleeve gastrectomy reveals the plasticity of the human gastric epithelium
Abstract Gastrin is secreted following a rise in gastric pH, leading to gastric acid secretion. Sleeve gastrectomy (SG), a bariatric surgery where 80% of the gastric corpus is excised, presents a challenge for gastric pH homeostasis. Using histology, and single-cell RNA sequencing of the gastric epi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56135-y |
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| author | Amit Elad Botros Moalem Dana Sender Aya Bardugo Ki-Suk Kim Yhara Arad Haya Benhayon Ayelet Gal Etzyoni Nehemia Greenstein Aviv Halfon Sarah Knapp Michelle Malis Bailey Peck Itia Samuel Amram Kupietzky Saleh Daher Esther Forkosh David Hakimian Tiberiu Hershcovici Nadav Ilani Lior Katz Moshe Rottenstreich Elez Vainer Yuval Ishay Eitan Zlotnick Abed Nasereddin Idid Shiff Ariel Benson Ronit Grinbaum Siddhartha Mishra Shlomi Kotler Linda C. Samuelson Darleen A. Sandoval Rachel Ben-Haroush Schyr Danny Ben-Zvi |
| author_facet | Amit Elad Botros Moalem Dana Sender Aya Bardugo Ki-Suk Kim Yhara Arad Haya Benhayon Ayelet Gal Etzyoni Nehemia Greenstein Aviv Halfon Sarah Knapp Michelle Malis Bailey Peck Itia Samuel Amram Kupietzky Saleh Daher Esther Forkosh David Hakimian Tiberiu Hershcovici Nadav Ilani Lior Katz Moshe Rottenstreich Elez Vainer Yuval Ishay Eitan Zlotnick Abed Nasereddin Idid Shiff Ariel Benson Ronit Grinbaum Siddhartha Mishra Shlomi Kotler Linda C. Samuelson Darleen A. Sandoval Rachel Ben-Haroush Schyr Danny Ben-Zvi |
| author_sort | Amit Elad |
| collection | DOAJ |
| description | Abstract Gastrin is secreted following a rise in gastric pH, leading to gastric acid secretion. Sleeve gastrectomy (SG), a bariatric surgery where 80% of the gastric corpus is excised, presents a challenge for gastric pH homeostasis. Using histology, and single-cell RNA sequencing of the gastric epithelium in 12 women, we observed that SG is associated with an increase in a sub-population of acid-secreting parietal cells that overexpress respiratory enzymes and an increase in histamine-secreting enterochromaffin-like cells (ECLs). ECLs of SG-operated patients overexpressed genes coding for biosynthesis of neuropeptides and serotonin. Mathematical modeling showed that pH homeostasis by gastrin is analogous to non-linear proportional and integral control, that drives adaptation of the epithelium to acid-secretion demand. Quantitative model predictions were validated in patients. The results demonstrate human gastric epithelium remodeling following SG at the molecular and cellular levels, and more generally how trophic hormones enable robust adaptation of tissue function to meet physiological demand. |
| format | Article |
| id | doaj-art-d39ecddb99004a56beb5e156f3ab9359 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d39ecddb99004a56beb5e156f3ab93592025-01-26T12:42:11ZengNature PortfolioNature Communications2041-17232025-01-0116111210.1038/s41467-025-56135-ySleeve gastrectomy reveals the plasticity of the human gastric epitheliumAmit Elad0Botros Moalem1Dana Sender2Aya Bardugo3Ki-Suk Kim4Yhara Arad5Haya Benhayon6Ayelet Gal Etzyoni7Nehemia Greenstein8Aviv Halfon9Sarah Knapp10Michelle Malis11Bailey Peck12Itia Samuel13Amram Kupietzky14Saleh Daher15Esther Forkosh16David Hakimian17Tiberiu Hershcovici18Nadav Ilani19Lior Katz20Moshe Rottenstreich21Elez Vainer22Yuval Ishay23Eitan Zlotnick24Abed Nasereddin25Idid Shiff26Ariel Benson27Ronit Grinbaum28Siddhartha Mishra29Shlomi Kotler30Linda C. Samuelson31Darleen A. Sandoval32Rachel Ben-Haroush Schyr33Danny Ben-Zvi34Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Physiology, University of Tennessee Health Science CenterDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Surgery, University of MichiganDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Surgery, University of MichiganDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, The Faculty of Medicine, Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemGenomics Applications Laboratory, Core Research Facility, Faculty of Medicine, The Hebrew University of JerusalemGenomics Applications Laboratory, Core Research Facility, Faculty of Medicine, The Hebrew University of JerusalemInstitute of Gastroenterology and Liver Disease, Hadassah University Medical Center, The Faculty of Medicine, Hebrew University of JerusalemDepartment of Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, The Faculty of Medicine, Hebrew University of JerusalemSeminar for Applied Mathematics, ETHThe Racah Institute of Physics, The Hebrew University of JerusalemDepartment of Molecular and Integrative Physiology, University of MichiganDepartment of Pediatrics, University of ColoradoDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel Canada, The Faculty of Medicine, The Hebrew University of JerusalemAbstract Gastrin is secreted following a rise in gastric pH, leading to gastric acid secretion. Sleeve gastrectomy (SG), a bariatric surgery where 80% of the gastric corpus is excised, presents a challenge for gastric pH homeostasis. Using histology, and single-cell RNA sequencing of the gastric epithelium in 12 women, we observed that SG is associated with an increase in a sub-population of acid-secreting parietal cells that overexpress respiratory enzymes and an increase in histamine-secreting enterochromaffin-like cells (ECLs). ECLs of SG-operated patients overexpressed genes coding for biosynthesis of neuropeptides and serotonin. Mathematical modeling showed that pH homeostasis by gastrin is analogous to non-linear proportional and integral control, that drives adaptation of the epithelium to acid-secretion demand. Quantitative model predictions were validated in patients. The results demonstrate human gastric epithelium remodeling following SG at the molecular and cellular levels, and more generally how trophic hormones enable robust adaptation of tissue function to meet physiological demand.https://doi.org/10.1038/s41467-025-56135-y |
| spellingShingle | Amit Elad Botros Moalem Dana Sender Aya Bardugo Ki-Suk Kim Yhara Arad Haya Benhayon Ayelet Gal Etzyoni Nehemia Greenstein Aviv Halfon Sarah Knapp Michelle Malis Bailey Peck Itia Samuel Amram Kupietzky Saleh Daher Esther Forkosh David Hakimian Tiberiu Hershcovici Nadav Ilani Lior Katz Moshe Rottenstreich Elez Vainer Yuval Ishay Eitan Zlotnick Abed Nasereddin Idid Shiff Ariel Benson Ronit Grinbaum Siddhartha Mishra Shlomi Kotler Linda C. Samuelson Darleen A. Sandoval Rachel Ben-Haroush Schyr Danny Ben-Zvi Sleeve gastrectomy reveals the plasticity of the human gastric epithelium Nature Communications |
| title | Sleeve gastrectomy reveals the plasticity of the human gastric epithelium |
| title_full | Sleeve gastrectomy reveals the plasticity of the human gastric epithelium |
| title_fullStr | Sleeve gastrectomy reveals the plasticity of the human gastric epithelium |
| title_full_unstemmed | Sleeve gastrectomy reveals the plasticity of the human gastric epithelium |
| title_short | Sleeve gastrectomy reveals the plasticity of the human gastric epithelium |
| title_sort | sleeve gastrectomy reveals the plasticity of the human gastric epithelium |
| url | https://doi.org/10.1038/s41467-025-56135-y |
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