2006 Fiscal Year Final Research Report Summary
Identification of gastrointestinal epithelial stem cell and development of regeneration therapy for LBD
| Project/Area Number |
16209024
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | KEIO UNIVERSITY |
|---|
Principal Investigator |
HIBI Toshifumi Keio University, School of Medicine, Professor, 医学部, 教授 (50129623)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
WATANABE Mamoru Tokyo Medical & Dental University, Dept of Medicine, Professor, 医学部, 教授 (10175127)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Keywords | intestinal epithelial cell / stem cell / musashi-1 / inflammatory bowel disease / regeneration of mucosa / β-catenin / WNT |
|---|
| Research Abstract |
Epithelial renewal occurs in the crypts through a coordinated series of events involving proliferation, differentiation and migration toward the intestinal lumen. It was believed that pluripotent stem cells were located at the lower third of the crypt and generated differentiated cells, such as intestinal epithelial cells, enteroendocrine cells, paneth cells and goblet cells. However, their manner of proliferation and differentiation remains unknown because they lack specific markers and methods of purification and culture. In this study, we propose a new technique to enrich epithelial stem cells and evaluate their phenotype.
We have separated crypts and villi from adult murine small intestine, and have shown that dephosphorylated β catenin and musashi-1 was enriched in crypts fraction. Crypt epithelial cells contained increased numbers of side population (SP) cells and as compared with vinous epithelial cells. In adult intestinal epithelial cells, SP cells have higher amounts of ABCG-2 as compared with main population (MP) cells. Fetal intestinal epithelial cells contained large numbers of SP cells. Dephosphorylated f3 catenin was enriched in SP cells as compared with MP cells.
Then, we focused on WNT/β catenin signaling pathway, and generated TOPGFP mice in which this signaling pathway could be visualized. In these mice, TOPGFP high cells expressed immature markers such as Musashi-1, c-myc. We sorted GFP+ cells from GFP-cells using flow cytometry and compared the expression of various markers in these populations using microarray. Several genes were found to be expressed differentially in GFP+ cells and GFP-cells. These results suggested that TOPGFP high cells were putative stem cells of intestinal epithelia.
|
Research Products
(12 results)
-
-
-
-
-
-
[Journal Article] Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients.2007
Author(s)
Matsuoka K, Iwao Y, Mori T, Sakuraba A, Yajitna T, Hisamatsu T, Okamoto S, Morohoshi Y, Izumiya M, Ichikawa H, Sato T, Inoue N, Ogata H, Hibi T.
-
Journal Title
Am J Gastroenterol 102 (2)
Pages: 331-337
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Journal Article] Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis.2006
Author(s)
Morohoshi Y, Matsuoka K, Chinen H, Kamada N, Sato T, Hisamatsu T, Okamoto S, Inoue N, Takaishi H, Ogata H, Iwao Y, Hibi T
-
Journal Title
J Gastroenterol 41 (4)
Pages: 318-324
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] Nonpathogenic Escherichia coli strain Nissle 1917 prevents murine acute and chronic colitis.2005
Author(s)
Kamada N, Inoue N, Hisamatsu T, Okamoto S, Matsuoka K, Sato T, Chinen H, Su Hong K, Yamada T, Suzuki Y, Suzuki T, Watanabe N, Tsuchimoto K, Hibi T.
-
Journal Title
Inflamm Bowel Dis 11 (5)
Pages: 455-463
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine.2005
Author(s)
Matsumoto T, Okamoto R, Yajima T, Mori T, Okamoto S, Ikeda Y, Mukai M, Yamazaki M, Oshima S, Tsuchiya K, Nakamura T, Kanai T, Okano H, Inazawa J, Hibi T, Watanabe M.
-
Journal Title
Gastroenterology 127 (7)
Pages: 1851-1867
Description
「研究成果報告書概要(欧文)」より
