第716回 生医研セミナー(多階層生体防御システム研究拠点)
新学術領域「生殖細胞のエピゲノムダイナミクスとその制御」、
「動物における配偶子産生システムの制御」合同セミナー


下記の通り、アメリカ・テキサス大学のJohn R. McCarrey先生によるセミナーを開催致します。
講演は英語で行われます。皆様のご来聴を心より歓迎いたします。

演題

Two privileged cell types - germ cells and stem cells –maintain enhanced genetic integrity.
(Seminar in English)

演者

Prof. John R. McCarrey
University of Texas, San Antonio, USA

日時

2016年 5月17日(火) May 17 (Tue), 2016
17:00~18:00

場所

病院キャンパス内 総合研究棟1階 セミナー室105
以下の地図の1番です。
(https://www.kyushu-u.ac.jp/f/27234/hospital_jp.pdf)

Seminar Room 105, 1F, Biomedical Research Station
No.1 on the following linked map.
(https://www.kyushu-u.ac.jp/f/27240/hospital_en.pdf)

要旨

In 1977, T.B.L. Kirkwood proposed the “Disposable Soma Theory” which posits that because germ cells and early embryonic cells (and, by modern extension, pluripotent stem cells) normally give rise to either entire subsequent generations or to large populations of subsequent cells within an individual body, it is evolutionarily advantageous for these cells to employ mechanisms that maintain an enhanced level of genetic integrity, even if this requires the expenditure of additional energy. We have used the “Big Blue” lacI mutation-reporter transgene system to confirm that both male and female germ cells maintain enhanced genetic integrity relative to that detected in somatic cells from the same individual. We also tracked mutation frequencies in donor somatic cells and in embryos produced by somatic cell nuclear transfer (cloning) and found that the mechanism regulating genetic integrity is subject to epigenetic reprogramming. We confirmed this by conducting direct comparisons of mutation frequencies in pluripotent and differentiated cell populations that shared a common origin and genetic identity. Further we found that transitions between pluripotent and differentiated cellular states, or vice versa, are accompanied by dynamic transformations in the relative stringency at which genetic integrity is maintained. We then tested the hypothesis that pluripotent cells are more resistant than differentiated cells to mutagenic effects by challenging each with the chemotherapeutic agent, methyl mathanesulfonate (MMS) and detecting significantly greater increases in mutation frequencies in exposed differentiated cells than in exposed pluripotent cells. Finally, to elucidate the mechanistic link between pluripotency and enhanced maintenance of genetic integrity, we mined existing databases describing gene expression in pluripotent and differentiated cell types and found significant differential expression of “genetic integrity” (DNA repair and cell death) genes in these cell types. We then analyzed databases describing cistromes of master pluripotency factors in ES and iPS cell types, which revealed abundant direct and indirect interactions between the pluripotency and genetic integrity gene networks in these cells. Taken together, these results confirm and extend the Disposable Soma Theory and indicate that maintenance of enhanced genetic integrity is a fundamental characteristic of both germ cells and pluripotent cells.

連絡先

生体防御医学研究所 エピゲノム制御学分野 佐々木 裕之
Division of Epigenomics and Development, MIB, Hiroyuki SASAKI
電話:092-642-6759

医学研究院 ヒトゲノム幹細胞医学分野 林 克彦
Developmental Stem Cell Biology, Faculty of Medical Sciences, Katsuhiko HAYASHI
電話:092-642-4844