2022 Fiscal Year Final Research Report
Elucidation of oxygen metabolism regulation in Spermatogonial Stem cells.
| Project/Area Number |
20K06445
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 42030:Animal life science-related
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Keywords | 活性酸素 |
|---|
| Outline of Final Research Achievements |
In this study we have done 4 subjects.(1)mechanism of ROS hypoxic response in spermatogonial stem cells (SSCs).(2)mechanism of ROS production in spermatogonial stem cells.(3)Target genes which works under hypoxic response.(4)HIF1A and CMYC genes whose deficiency exacerbated self-renewal efficiency. We report the critical role of oxygen on ROS-induced self-renewal. NOX1-derived ROS were significantly reduced, and Nox1-deficient SSCs proliferated poorly under hypoxia but normally under normoxia. NOX1-derived ROS also influenced hypoxic response in vivo because Nox1-deficient undifferentiated spermatogonia showed significantly reduced expression of HIF1A, a master transcription factor for hypoxic response. Hypoxia-induced poor proliferation occurred despite activation of MYC and suppression of CDKN1A by HIF1A, whose deficiency exacerbated self-renewal efficiency. These results underscore the importance of ROS origin and oxygen tension on SSC self-renewal.
|
| Free Research Field |
精子幹細胞
|
| Academic Significance and Societal Importance of the Research Achievements |
これまで精子幹細胞の自己複製におけるROSの役割については我々のグループが最先端の研究成果を報告してきた。他の研究グループではROSについての研究はなされていない。自己複製における低酸素の役割については血液幹細胞やES細胞などでは報告されているものの、通常は低酸素が幹細胞の増殖を刺激する方向で働くのに対して、GS細胞は増殖の低下が起こる。恐らく酸素に対する反応性が精子幹細胞では異なっていることが予想される。その意味で、今回の低酸素のGS細胞のROS発生や自己複製分裂に対する影響の解析は他の幹細胞との比較の上でも、これまでの研究を取りまとめる意味でも重要なステップであり、ユニークなものである。
|
