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Effects of heat shock on survival, proliferation and differentiation of embryonic stem cell-derived neural stem cells

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Effects of heat shock on survival,

proliferation and differentiation of embryonic stem cell‑derived neural stem cells

著者 大森 啓之

発行年 2014‑03‑25

その他のタイトル 胚性幹細胞由来神経幹細胞の生存・増殖・分化に対 する温熱刺激の影響

学位授与機関 首都大学東京 学位授与番号 22604A457

URL http://hdl.handle.net/10748/6932

(2)

Effects of heat shock on survival, proliferation and differentiation of embryonic stem cell-derived

neural stem cells

胚性幹細胞由来神経幹細胞の生存・増殖・分化に 対する温熱刺激の影響

首都大学東京大学院

人間健康科学研究科 博士後期課程 人間健康科学専攻 フロンティアヘルスサイエンス学域

大森 啓之

(3)

ABSTRACT

Hyperthermia during pregnancy is a significant cause of reproductive problems ranging from

abortion to congenital defects of the central nervous system (CNS), including neural tube defects and

microcephaly. Neural stem cells (NSCs) can proliferate and differentiate into neurons and glia,

playing a key role in the formation of the CNS. Here, we examined the effects of heat shock on

homogeneous proliferating NSCs derived from mouse embryonic stem cells. After heat shock at

42°C for 20 min, the proliferating NSCs continued to proliferate, although subtle changes were

observed in gene expression and cell survival and proliferation. In contrast, heat shock at 43°C caused

a variety of responses: the up-regulation of genes encoding heat shock proteins (HSP), induction of

apoptosis, temporal inhibition of cell proliferation and retardation of differentiation. Finally, effects of

heat shock at 44°C were severe, with almost all cells disappearing and the remaining cells losing the

capacity to proliferate and differentiate. These temperature-dependent effects of heat shock on NSCs

may be valuable in elucidating the mechanisms by which hyperthermia during pregnancy causes

various reproductive problems.

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