Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells.
Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells.
复制标题
DOI：
10.1038/srep35680
复制
发表时间：
2016-11-02
影响因子：
4.6
通讯作者：
Saito MK
中科院分区：
文献类型：
--
作者：
Ohta R;Niwa A;Taniguchi Y;Suzuki NM;Toga J;Yagi E;Saiki N;Nishinaka-Arai Y;Okada C;Watanabe A;Nakahata T;Sekiguchi K;Saito MK
从人多能干细胞（human pluripotent stem cells，hPSC）定向分化获得高纯度的分化细胞是其临床应用的重要步骤。在应该优化的各种条件中，细胞外基质（ECM）在分化过程中的确切作用和贡献相对不清楚。在这里，使用层粘连蛋白411（LM 411-E8）的短片段，一种主要在血管内皮基底膜中表达的ECM，我们证明了定义的ECM的定向转换稳健地产生高度纯化（>95%）的内皮祖细胞（PSC-EPC），而不以整合素-层粘连蛋白轴依赖性方式从hPSC进行细胞分选。单细胞RNA-seq分析显示，LM 411-E8解决了细胞间的转录异质性，并护送祖细胞进入适当的分化途径。PSC-EPCs在体内和体外均产生功能性内皮细胞。因此，我们建议，顺序切换定义的矩阵是一个重要的概念，引导细胞走向所需的命运。
Obtaining highly purified differentiated cells via directed differentiation from human pluripotent stem cells (hPSCs) is an essential step for their clinical application. Among the various conditions that should be optimized, the precise role and contribution of the extracellular matrix (ECM) during differentiation are relatively unclear. Here, using a short fragment of laminin 411 (LM411-E8), an ECM predominantly expressed in the vascular endothelial basement membrane, we demonstrate that the directed switching of defined ECMs robustly yields highly-purified (>95%) endothelial progenitor cells (PSC-EPCs) without cell sorting from hPSCs in an integrin-laminin axis-dependent manner. Single-cell RNA-seq analysis revealed that LM411-E8 resolved intercellular transcriptional heterogeneity and escorted the progenitor cells to the appropriate differentiation pathway. The PSC-EPCs gave rise to functional endothelial cells both in vivo and in vitro. We therefore propose that sequential switching of defined matrices is an important concept for guiding cells towards desired fate.
登录
查看更多内容
影响因子：
48
作者：
Kurian, Leo;Sancho-Martinez, Ignacio;Nivet, Emmanuel;Aguirre, Aitor;Moon, Krystal;Pendaries, Caroline;Volle-Challier, Cecile;Bono, Francoise;Herbert, Jean-Marc;Pulecio, Julian;Xia, Yun;Li, Mo;Montserrat, Nuria;Ruiz, Sergio;Dubova, Ilir;Rodriguez, Concepcion;Denli, Ahmet M.;Boscolo, Francesca S.;Thiagarajan, Rathi D.;Gage, Fred H.;Loring, Jeanne F.;Laurent, Louise C.;Izpisua Belmonte, Juan Carlos
通讯作者：
Izpisua Belmonte, Juan Carlos
影响因子：
5.9
作者：
Doi, Daisuke;Samata, Bumpei;Katsukawa, Mitsuko;Kikuchi, Tetsuhiro;Morizane, Asuka;Ono, Yuichi;Sekiguchi, Kiyotoshi;Nakagawa, Masato;Parmar, Malin;Takahashi, Jun
通讯作者：
Takahashi, Jun
影响因子：
21.3
作者：
Ditadi A;Sturgeon CM;Tober J;Awong G;Kennedy M;Yzaguirre AD;Azzola L;Ng ES;Stanley EG;French DL;Cheng X;Gadue P;Speck NA;Elefanty AG;Keller G
通讯作者：
Keller G
影响因子：
7.7
作者：
Stenzel, Denise;Franco, Claudio A.;Gerhardt, Holger
通讯作者：
Gerhardt, Holger
影响因子：
2.7
作者：
Chaudhury, Hera;Raborn, Eric;Hirschi, Karen K.
通讯作者：
Hirschi, Karen K.