Restoration of keratinocytic phenotypes in autonomous trisomy-rescued cells.
Restoration of keratinocytic phenotypes in autonomous trisomy-rescued cells.
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DOI：
10.1186/s13287-021-02448-w
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发表时间：
2021-08-25
影响因子：
7.5
通讯作者：
Umezawa A
中科院分区：
文献类型：
--
作者：
Tanuma-Takahashi A;Inoue M;Kajiwara K;Takagi R;Yamaguchi A;Samura O;Akutsu H;Sago H;Kiyono T;Okamoto A;Umezawa A
人类21号染色体的额外拷贝可以改变细胞表型以及免疫和代谢系统。唐氏综合症与许多健康相关的问题和年龄相关的疾病，包括皮肤病异常。然而，很少有研究集中在21三体（T21）对表皮干细胞和祖细胞功能障碍的影响。在这里，我们通过区分来自21三体诱导的多能干细胞（T21-iPSC）和自主拯救的21三体诱导的多能干细胞（D21-iPSC）的细胞来研究唐氏综合征和整倍体细胞之间的角质形成细胞特征的差异。采用我们的用于T21-iPSC和D21-iPSC的角质形成细胞分化的方案。为了增殖T21-和D21-iPSC衍生的角质形成细胞和细胞片层形成，随着生长速率降低，在小鼠饲养细胞上引入补充有Rho激酶抑制剂的培养基。在传代之前，进行具有差异分散酶反应性的角质形成细胞群体的选择。进行三维（3D）气液界面以评价iPSC衍生的角质形成细胞分化和形成复层鳞状上皮的能力。与三体21-iPSC相比，三体拯救的二体性21-iPSC能够表皮分化并在分化时表达角化细胞标志物如KRT 14和TP 63。iPSC衍生的角质形成细胞的寿命可以在含有Rho激酶抑制剂的培养基中的小鼠饲养细胞上成功地延长至超过34个群体倍增时间超过160天。二体性iPSC衍生的角质形成细胞的基于分散的纯化有助于表皮片形成。具有延长寿命的三体挽救的二体性21-iPSC衍生的角质形成细胞与真皮成纤维细胞组分组合产生3D皮肤。来源于自主三体拯救的iPSC的角质形成细胞具有分层的能力，用于制造具有恢复角质形成细胞功能的3D皮肤。在线版本包含补充材料，可通过10.1186/s13287-021-02448-w获得。
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). 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. 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. Keratinocytes derived from autonomous trisomy-rescued iPSC have the ability of stratification for manufacturing 3D skin with restoration of keratinocytic functions. The online version contains supplementary material available at 10.1186/s13287-021-02448-w.
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影响因子：
168.9
作者：
Hasle, H;Clemmensen, IH;Mikkelsen, M
通讯作者：
Mikkelsen, M
影响因子：
5
作者：
Fuchs, Claudia;Ciani, Elisabetta;Bartesaghi, Renata
通讯作者：
Bartesaghi, Renata
DOI：
10.1016/s0074-7750(10)39004-5
发表时间：
2010-01-01
期刊：
INTERNATIONAL REVIEW OF RESEARCH IN MENTAL RETARDATION, VOL 39: HEALTH ISSUES AMONG PERSONS WITH DOWN SYNDROME
影响因子：
--
作者：
Esbensen, Anna J.
通讯作者：
Esbensen, Anna J.
影响因子：
3.7
作者：
Gonzales PK;Roberts CM;Fonte V;Jacobsen C;Stein GH;Link CD
通讯作者：
Link CD
影响因子：
11.1
作者：
Hibaoui, Youssef;Grad, Iwona;Letourneau, Audrey;Sailani, M. Reza;Dahoun, Sophie;Santoni, Federico A.;Gimelli, Stefania;Guipponi, Michel;Pelte, Marie Francoise;Bena, Frederique;Antonarakis, Stylianos E.;Feki, Anis
通讯作者：
Feki, Anis