2021 Fiscal Year Final Research Report
Oocyte production with the set of ovarian follcle progenitors induced from mouse ESCs
Project/Area Number |
19K06678
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 44020:Developmental biology-related
|
Research Institution | Kyushu University |
Principal Investigator |
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Keywords | マウスES細胞 / 卵巣オルガノイド / 卵巣サブポピュレーション / 再構築卵胞 |
Outline of Final Research Achievements |
I induced ovarian somatic cells from female mouse ESCs by the appropriate treatment with molecules that function in vivo. Single-cell RNA-seq analysis showed that cells differentiated into all ovarian somatic cell subpopulations. We named these cells FOSLCs (Fetal Ovarian Somatic cell-Like Cells). Subsequently, we reconstructed ovarioids by reaggregating Primordial Germ Cell Like Cells (PGCLCs) and FOSCLs. In ovarioids, cells recapitulated ovarian development. On day 23, ovarioid forms numerous follicles where oocytes were surrounded by multilayered granulosa cells and theca cells, both of which are known to play central roles in female hormone secretion. Then, oocytes developed into MII oocytes, by in vitro growth and in vitro maturation culture. We also confirmed the functionality of MII oocytes by in vitro fertilization. Fertilized embryos at the 2-cell stage were transplanted into pseudopregnant mice, pups were obtained.
|
Free Research Field |
発生生物学
|
Academic Significance and Societal Importance of the Research Achievements |
本研究により初めて卵巣オルガノイドが多能性幹細胞から再構築された。卵巣と精巣の原基である未分化生殖巣を構成する細胞は始原生殖細胞(PGC)と体細胞に分けられ、発生は体細胞に主導される。これまでにPGC様細胞はマウス、ヒトなどの多能性肝細胞から誘導されたが、体細胞の誘導研究は進んでいなかった。本研究は、マウスES細胞から生殖巣体細胞を誘導しPGC様細胞と生殖巣(卵巣)を構築し卵子を作出できた点で学術的及び社会的に意義ぶかい。本研究の成果をもとに、ヒトなど多くの動物の生殖巣オルガノイドを利用してのヒトなどの種特異的な生殖細胞/生殖巣の形成に関する研究が進ことが期待される。
|