Cargando…
Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells
Although intestinal homeostasis is maintained by intestinal stem cells (ISCs), regeneration is impaired upon aging. Here, we first uncover changes in intestinal architecture, cell number, and cell composition upon aging. Second, we identify a decline in the regenerative capacity of ISCs upon aging b...
| Autores principales: | , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2017
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987258/ https://www.ncbi.nlm.nih.gov/pubmed/28297666 http://dx.doi.org/10.1016/j.celrep.2017.02.056 |
| _version_ | 1783329078384787456 |
|---|---|
| author | Nalapareddy, Kodandaramireddy Nattamai, Kalpana J. Kumar, Rupali S. Karns, Rebekah Wikenheiser-Brokamp, Kathryn A. Sampson, Leesa L. Mahe, Maxime M. Sundaram, Nambirajan Yacyshyn, Mary-Beth Yacyshyn, Bruce Helmrath, Michael A. Zheng, Yi Geiger, Hartmut |
| author_facet | Nalapareddy, Kodandaramireddy Nattamai, Kalpana J. Kumar, Rupali S. Karns, Rebekah Wikenheiser-Brokamp, Kathryn A. Sampson, Leesa L. Mahe, Maxime M. Sundaram, Nambirajan Yacyshyn, Mary-Beth Yacyshyn, Bruce Helmrath, Michael A. Zheng, Yi Geiger, Hartmut |
| author_sort | Nalapareddy, Kodandaramireddy |
| collection | PubMed |
| description | Although intestinal homeostasis is maintained by intestinal stem cells (ISCs), regeneration is impaired upon aging. Here, we first uncover changes in intestinal architecture, cell number, and cell composition upon aging. Second, we identify a decline in the regenerative capacity of ISCs upon aging because of a decline in canonical Wnt signaling in ISCs. Changes in expression of Wnts are found in stem cells themselves and in their niche, including Paneth cells and mesenchyme. Third, reactivating canonical Wnt signaling enhances the function of both murine and human ISCs and, thus, ameliorates aging-associated phenotypes of ISCs in an organoid assay. Our data demonstrate a role for impaired Wnt signaling in physiological aging of ISCs and further identify potential therapeutic avenues to improve ISC regenerative potential upon aging. |
| format | Online Article Text |
| id | pubmed-5987258 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-59872582018-06-05 Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells Nalapareddy, Kodandaramireddy Nattamai, Kalpana J. Kumar, Rupali S. Karns, Rebekah Wikenheiser-Brokamp, Kathryn A. Sampson, Leesa L. Mahe, Maxime M. Sundaram, Nambirajan Yacyshyn, Mary-Beth Yacyshyn, Bruce Helmrath, Michael A. Zheng, Yi Geiger, Hartmut Cell Rep Article Although intestinal homeostasis is maintained by intestinal stem cells (ISCs), regeneration is impaired upon aging. Here, we first uncover changes in intestinal architecture, cell number, and cell composition upon aging. Second, we identify a decline in the regenerative capacity of ISCs upon aging because of a decline in canonical Wnt signaling in ISCs. Changes in expression of Wnts are found in stem cells themselves and in their niche, including Paneth cells and mesenchyme. Third, reactivating canonical Wnt signaling enhances the function of both murine and human ISCs and, thus, ameliorates aging-associated phenotypes of ISCs in an organoid assay. Our data demonstrate a role for impaired Wnt signaling in physiological aging of ISCs and further identify potential therapeutic avenues to improve ISC regenerative potential upon aging. 2017-03-14 /pmc/articles/PMC5987258/ /pubmed/28297666 http://dx.doi.org/10.1016/j.celrep.2017.02.056 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| spellingShingle | Article Nalapareddy, Kodandaramireddy Nattamai, Kalpana J. Kumar, Rupali S. Karns, Rebekah Wikenheiser-Brokamp, Kathryn A. Sampson, Leesa L. Mahe, Maxime M. Sundaram, Nambirajan Yacyshyn, Mary-Beth Yacyshyn, Bruce Helmrath, Michael A. Zheng, Yi Geiger, Hartmut Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells |
| title | Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells |
| title_full | Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells |
| title_fullStr | Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells |
| title_full_unstemmed | Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells |
| title_short | Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells |
| title_sort | canonical wnt signaling ameliorates aging of intestinal stem cells |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987258/ https://www.ncbi.nlm.nih.gov/pubmed/28297666 http://dx.doi.org/10.1016/j.celrep.2017.02.056 |
| work_keys_str_mv | AT nalapareddykodandaramireddy canonicalwntsignalingamelioratesagingofintestinalstemcells AT nattamaikalpanaj canonicalwntsignalingamelioratesagingofintestinalstemcells AT kumarrupalis canonicalwntsignalingamelioratesagingofintestinalstemcells AT karnsrebekah canonicalwntsignalingamelioratesagingofintestinalstemcells AT wikenheiserbrokampkathryna canonicalwntsignalingamelioratesagingofintestinalstemcells AT sampsonleesal canonicalwntsignalingamelioratesagingofintestinalstemcells AT mahemaximem canonicalwntsignalingamelioratesagingofintestinalstemcells AT sundaramnambirajan canonicalwntsignalingamelioratesagingofintestinalstemcells AT yacyshynmarybeth canonicalwntsignalingamelioratesagingofintestinalstemcells AT yacyshynbruce canonicalwntsignalingamelioratesagingofintestinalstemcells AT helmrathmichaela canonicalwntsignalingamelioratesagingofintestinalstemcells AT zhengyi canonicalwntsignalingamelioratesagingofintestinalstemcells AT geigerhartmut canonicalwntsignalingamelioratesagingofintestinalstemcells |