2020 Fiscal Year Research-status Report
Defining the mechanism of epidermal stem cell heterogeneity in skin aging
| Project/Area Number |
20K22659
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| Research Institution | Kumamoto University |
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Principal Investigator |
Raja Erna 熊本大学, 国際先端医学研究機構, 特定事業研究員 (30770581)
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Keywords | stem cells / ECM / aging |
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| Outline of Annual Research Achievements |
We are characterizing the aging process in skin inter-follicular epidermal stem cells consisting of the fast-dividing and slow-cycling stem cells. We found that the fast-dividing stem cells were gradually lost in aging, but slow-cycling stem cells were maintained.
Global gene expression analysis indicated that aging fast-dividing stem cells have altered cell-adhesion and extracellular matrix (ECM) components, one of which was Fibulin-7. Fibulin-7 knock-out led to early loss of fast-dividing stem cells and defective wound healing, suggesting impaired regenerative skin capacity.
Mechanistically, we propose that Fibulin-7 binds to other ECM proteins to promote ECM integrity and suppress stress signaling thus regulating the balance of stem cells renewal and differentiation.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
In addition to reconfirmation and revision of previous data, we obtained some new data that could add further insight into the study. For example, differentiation changes during stem cells aging and also in the absence of Fibulin-7 in the skin stem cells extra-celullar matrix.
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| Strategy for Future Research Activity |
We plan to further examine the function of fibulin-7 in maintenance of ECM integrity and stem cells maintenance by proper renewal and differentiation process in the epidermis. We will attempt to identify which signaling pathway is relevant and where possible, to use small molecule inhibitors to promote or inhibit Fibulin-7 function in vitro and in vivo.
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| Causes of Carryover |
The remaining grant amount will be allocated for use in cell culture experiments, cell culture reagents, chemicals, antibodies, biochemical kits, and also animal husbandry costs.
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