タカギ　リヨウ   Takagi Riyou   高木　亮    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Restoration of keratinocytic phenotypes in autonomous trisomy-rescued cells.
掲載誌名	正式名：Stem cell research & therapy 略　 称：Stem Cell Res Ther ISSNコード：17576512/17576512
掲載区分	国外
巻・号・頁	12(1),pp.476
著者・共著者	TANUMA-TAKAHASHI Akiko†, INOUE Momoko, KAJIWARA Kazuhiro, TAKAGI Ryo, YAMAGUCHI Ayumi, SAMURA Osamu, AKUTSU Hidenori, SAGO Haruhiko, KIYONO Tohru, OKAMOTO Aikou, UMEZAWA Akhiro*
発行年月	2021/08
概要	BACKGROUND:An extra copy of chromosome 21 in humans can alter cellular phenotypes as well as immune and metabolic systems. Down syndrome is associated with many health-related problems and age-related disorders including dermatological abnormalities. However, few studies have focused on the impact of trisomy 21 (T21) on epidermal stem cells and progenitor cell dysfunction. Here, we investigated the differences in keratinocytic characteristics between Down syndrome and euploid cells by differentiating cells from trisomy 21-induced pluripotent stem cells (T21-iPSCs) and autonomous rescued disomy 21-iPSCs (D21-iPSCs).METHODS:Our protocol for keratinocytic differentiation of T21-iPSCs and D21-iPSCs was employed. For propagation of T21- and D21-iPSC-derived keratinocytes and cell sheet formation, the culture medium supplemented with Rho kinase inhibitor on mouse feeder cells was introduced as growth rate decreased. Before passaging, selection of a keratinocytic population with differential dispase reactivity was performed. Three-dimensional (3D) air-liquid interface was performed in order to evaluate the ability of iPSC-derived keratinocytes to differentiate and form stratified squamous epithelium.RESULTS:Trisomy-rescued disomy 21-iPSCs were capable of epidermal differentiation and expressed keratinocytic markers such as KRT14 and TP63 upon differentiation compared to trisomy 21-iPSCs. The lifespan of iPSC-derived keratinocytes could successfully be extended on mouse feeder cells in media containing Rho kinase inhibitor, to more than 34 population doublings over a period of 160 days. Dispase-based purification of disomy iPSC-derived keratinocytes contributed epidermal sheet formation. The trisomy-rescued disomy 21-iPSC-derived keratinocytes with an expanded lifespan generated 3D skin in combination with a dermal fibroblast component.CONCLUSIONS:Keratinocytes derived from autonomous trisomy-rescued iPSC have the ability of stratification for manufacturing 3D skin with res
DOI	10.1186/s13287-021-02448-w
PMID	34433490