Escape from Pluripotency via Inhibition of TGF-β/BMP and Activation of Wnt Signaling Accelerates Differentiation and Aging in hPSC Progeny Cells.
Escape from Pluripotency via Inhibition of TGF-β/BMP and Activation of Wnt Signaling Accelerates Differentiation and Aging in hPSC Progeny Cells.
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DOI：
10.1016/j.stemcr.2017.09.024
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发表时间：
2017-11-14
影响因子：
5.9
通讯作者：
Akamatsu W
中科院分区：
文献类型：
--
作者：
Fujimori K;Matsumoto T;Kisa F;Hattori N;Okano H;Akamatsu W
人类多能干细胞（hPSCs）在细胞替代疗法、药物开发和疾病建模方面具有潜在的应用价值。对于所有这些用途，有必要开发可重复的和强大的方案分化成所需的细胞类型。然而，分化方案仍然不稳定且效率低下，这使得最小化hPSC系间分化差异和获得纯化的终末分化细胞非常耗时。在这里，我们报告了一种简单的处理方法，用三个小分子——sb431542、dorsomorphine和chir99021——促进hPSC分化为三个胚层，并具有化学过渡胚体样状态（CTraS）。CTraS的诱导降低了人乳头状细胞（甚至是分化不利的人乳头状细胞）的先天分化倾向，并将其分化为终末分化细胞，特别是神经元。此外，CTraS的诱导在神经成熟的同时加速了体外病理表达。因此，CTraS可以促进人造血干细胞的潜在分化潜力，并有可能扩大人造血干细胞的实用性和适用性。CTraS诱导增强hPSC向三胚层分化无偏见CTraS诱导适用于广泛的hPSCs，即使没有集落选择通过CTraS建立强大的神经诱导方案用于hPSC疾病建模CTraS诱导促进体外病理表达随着成熟和衰老简单的三种小分子处理增强hPSC向三胚层分化，即CTraS。CTraS降低了人造血干细胞的先天分化倾向，并将其转变为终末分化。随着成熟和衰老，CTraS的诱导加速了体外病理表达。因此，CTraS可以发挥出hPSCs的潜在潜力。
Human pluripotent stem cells (hPSCs) represent a potentially valuable cell source for applications in cell replacement therapy, drug development, and disease modeling. For all these uses, it is necessary to develop reproducible and robust protocols for differentiation into desired cell types. However, differentiation protocols remain unstable and inefficient, which makes minimizing the differentiation variance among hPSC lines and obtaining purified terminally differentiated cells extremely time consuming. Here, we report a simple treatment with three small molecules—SB431542, dorsomorphine, and CHIR99021—that enhanced hPSC differentiation into three germ layers with a chemically transitional embryoid-body-like state (CTraS). Induction of CTraS reduced the innate differentiation propensities of hPSCs (even unfavorably differentiated hPSCs) and shifted their differentiation into terminally differentiated cells, particularly neurons. In addition, CTraS induction accelerated in vitro pathological expression concurrently with neural maturation. Thus, CTraS can promote the latent potential of hPSCs for differentiation and potentially expand the utility and applicability of hPSCs. CTraS induction enhances hPSC differentiation into three germ layers without bias CTraS induction is applicable to a wide range of hPSCs even without colony selection Developing a robust neural induction protocol via CTraS for hPSC disease modeling CTraS induction promotes in vitro pathological expression with maturation and aging Simple treatment with three small molecules enhanced hPSC differentiation into three germ layers, namely CTraS. CTraS reduced the innate differentiation propensities of hPSCs and shifted them into terminal differentiations. CTraS induction accelerated in vitro pathological expression with maturation and aging. Thus, CTraS can bring out the latent potential of hPSCs.
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影响因子：
64.8
作者：
Kriks, Sonja;Shim, Jae-Won;Piao, Jinghua;Ganat, Yosif M.;Wakeman, Dustin R.;Xie, Zhong;Carrillo-Reid, Luis;Auyeung, Gordon;Antonacci, Chris;Buch, Amanda;Yang, Lichuan;Beal, M. Flint;Surmeier, D. James;Kordower, Jeffrey H.;Tabar, Viviane;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
3.7
作者：
Kobayashi Y;Okada Y;Itakura G;Iwai H;Nishimura S;Yasuda A;Nori S;Hikishima K;Konomi T;Fujiyoshi K;Tsuji O;Toyama Y;Yamanaka S;Nakamura M;Okano H
通讯作者：
Okano H
影响因子：
23.9
作者：
Miller JD;Ganat YM;Kishinevsky S;Bowman RL;Liu B;Tu EY;Mandal PK;Vera E;Shim JW;Kriks S;Taldone T;Fusaki N;Tomishima MJ;Krainc D;Milner TA;Rossi DJ;Studer L
通讯作者：
Studer L
影响因子：
20.3
作者：
Ng, ES;Davis, RP;Elefanty, AG
通讯作者：
Elefanty, AG
影响因子：
23.9
作者：
Li, Wenlin;Li, Ke;Wei, Wanguo;Ding, Sheng
通讯作者：
Ding, Sheng