Top-Down Inhibition of BMP Signaling Enables Robust Induction of hPSCs Into Neural Crest in Fully Defined, Xeno-free Conditions.
Top-Down Inhibition of BMP Signaling Enables Robust Induction of hPSCs Into Neural Crest in Fully Defined, Xeno-free Conditions.
复制标题
DOI：
10.1016/j.stemcr.2017.08.008
复制
发表时间：
2017-10-10
影响因子：
5.9
通讯作者：
Andrews PW
中科院分区：
文献类型：
--
作者：
Hackland JOS;Frith TJR;Thompson O;Marin Navarro A;Garcia-Castro MI;Unger C;Andrews PW
神经嵴发育的缺陷与许多人类疾病有关，但有关人类神经嵴形成的信息主要取决于模式生物的外推。人多能干细胞（hPSC）可以分化成神经嵴的体外对应物，并且在此过程中需要一些已知在体内诱导神经嵴形成的信号。然而，目前使用的协议往往会产生可变的结果，并没有达成共识，以最佳的神经嵴分化所需的精确信号。使用完全确定的培养系统，我们现在已经发现hPSC向神经嵴的有效分化取决于BMP信号传导的精确水平，其容易受到内源性BMP产生的波动的影响。我们提出了一种控制这种现象的方法，并可应用于其他系统，其中内源性信号也可以影响分化方案的结果。hPSC向神经嵴培养物的完全限定的和无异种的分化表现出对BMP的响应，其类似于体内外胚层图案化。内源性BMP信号传导可以影响分化的再现性。控制内源性BMP的可变贡献的广泛适用的系统Hackland和同事已经开发了用于产生人神经嵴细胞的方法，其允许其在临床应用中使用。他们的方法允许通过管理细胞产生的信号的影响来更好地控制细胞的环境，这种方法可以应用于其他系统。
Defects in neural crest development have been implicated in many human disorders, but information about human neural crest formation mostly depends on extrapolation from model organisms. Human pluripotent stem cells (hPSCs) can be differentiated into in vitro counterparts of the neural crest, and some of the signals known to induce neural crest formation in vivo are required during this process. However, the protocols in current use tend to produce variable results, and there is no consensus as to the precise signals required for optimal neural crest differentiation. Using a fully defined culture system, we have now found that the efficient differentiation of hPSCs to neural crest depends on precise levels of BMP signaling, which are vulnerable to fluctuations in endogenous BMP production. We present a method that controls for this phenomenon and could be applied to other systems where endogenous signaling can also affect the outcome of differentiation protocols. Fully defined and xeno-free differentiation of hPSCs into neural crest Cultures exhibit a response to BMP that is analogous to ectodermal patterning in vivo Endogenous BMP signaling can affect reproducibility of differentiation A broadly applicable system that controls for variable contribution of endogenous BMP Hackland and colleagues have developed a method for the generation of human neural crest cells that allows their use in clinical applications. Their method allows for greater control over the environment of the cells by managing the influence of cell-produced signals, and this approach could be applied to other systems.
登录
查看更多内容
影响因子：
64.8
作者：
Chen, Wei;Jongkamonwiwat, Nopporn;Abbas, Leila;Eshtan, Sarah Jacob;Johnson, Stuart L.;Kuhn, Stephanie;Milo, Marta;Thurlow, Johanna K.;Andrews, Peter W.;Marcotti, Walter;Moore, Harry D.;Rivolta, Marcelo N.
通讯作者：
Rivolta, Marcelo N.
影响因子：
11.4
作者：
Sasai, Y;Lu, B;DeRobertis, EM
通讯作者：
DeRobertis, EM
影响因子：
14.8
作者：
Lee, Gabsang;Chambers, Stuart M.;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
46.9
作者：
Chambers, Stuart M.;Fasano, Christopher A.;Papapetrou, Eirini P.;Tomishima, Mark;Sadelain, Michel;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
64.8
作者：
Basch, ML;Bronner-Fraser, M;García-Castro, MI
通讯作者：
García-Castro, MI