Vitronectin-activated αvβ3 and αvβ5 integrin signalling specifies haematopoietic fate in human pluripotent stem cells.
Vitronectin-activated αvβ3 and αvβ5 integrin signalling specifies haematopoietic fate in human pluripotent stem cells.
复制标题
DOI：
10.1111/cpr.13012
复制
发表时间：
2021-04
影响因子：
8.5
通讯作者：
Cheng T
中科院分区：
文献类型：
--
作者：
Shen J;Zhu Y;Zhang S;Lyu S;Lyu C;Feng Z;Hoyle DL;Wang ZZ;Cheng T
玻连蛋白（VTN）已广泛用于维持和扩增人多能干细胞（hPSC）作为无饲养层条件。然而，VTN对hPSC分化的影响仍不清楚。在这里，我们研究了VTN在hPSC早期造血发育中的作用。应用化学定义的单层系统来研究不同基质或基底膜蛋白在hPSC的造血发育中的作用。通过整联蛋白拮抗剂研究整联蛋白信号传导在VTN介导的造血分化中的作用。最后，使用小干扰RNA敲低分化细胞中的整合素基因表达。我们发现，在VTN上的hPSC的造血分化比在也经常用于hPSC培养的基质胶上的造血分化有效得多。VTN在中胚层发育过程中促进内皮造血谱系的命运决定，以产生造血内皮（HE）。此外，我们证明了通过αvβ3和αvβ5整合素的信号是VTN促进造血分化所必需的。通过整联蛋白拮抗剂阻断αvβ3和αvβ5整联蛋白会损害HE的发生，但不会损害内皮细胞向造血细胞转化（EHT）。最后，通过敲低αv、β3或β5的表达，证实αvβ3和αvβ5两者对于早期造血分化协同作用。建立的基于VTN的hPSC造血分化单层系统为进一步研究参与人类造血发育的生态位信号提供了有价值的平台。与基质胶（MTG）相比，玻连蛋白（VTN）是中胚层获得更高的内皮造血潜能所必需的。VTN对早期造血的促进作用依赖于αvβ3和αvβ5整合素。抑制αvβ3和αvβ5会损害HE的发展，但不影响EHT。
Vitronectin (VTN) has been widely used for the maintenance and expansion of human pluripotent stem cells (hPSCs) as feeder‐free conditions. However, the effect of VTN on hPSC differentiation remains unclear. Here, we investigated the role of VTN in early haematopoietic development of hPSCs. A chemically defined monolayer system was applied to study the role of different matrix or basement membrane proteins in haematopoietic development of hPSCs. The role of integrin signalling in VTN‐mediated haematopoietic differentiation was investigated by integrin antagonists. Finally, small interfering RNA was used to knock down integrin gene expression in differentiated cells. We found that the haematopoietic differentiation of hPSCs on VTN was far more efficient than that on Matrigel that is also often used for hPSC culture. VTN promoted the fate determination of endothelial‐haematopoietic lineage during mesoderm development to generate haemogenic endothelium (HE). Moreover, we demonstrated that the signals through αvβ3 and αvβ5 integrins were required for VTN‐promoted haematopoietic differentiation. Blocking αvβ3 and αvβ5 integrins by the integrin antagonists impaired the development of HE, but not endothelial‐to‐haematopoietic transition (EHT). Finally, both αvβ3 and αvβ5 were confirmed acting synergistically for early haematopoietic differentiation by knockdown the expression of αv, β3 or β5. The established VTN‐based monolayer system of haematopoietic differentiation of hPSCs presents a valuable platform for further investigating niche signals involved in human haematopoietic development. Compared with Matrigel (MTG), vitronectin (VTN) was required for the mesoderm to acquire higher endothelial‐hematopoietic potential. The promoting effect of VTN on early hematopoiesis was dependent on αvβ3 and αvβ5 integrins. Inhibition of αvβ3 and αvβ5 impaired HE development without affecting EHT.
登录
查看更多内容
纤连蛋白与非常晚的抗原5通过纤连蛋白的相互作用诱导人造血细胞系中的程序性细胞死亡。
影响因子：
15.3
作者：
Sugahara, H;Kanakura, Y;Furitsu, T;Ishihara, K;Oritani, K;Ikeda, H;Kitayama, H;Ishikawa, J;Hashimoto, K;Kanayama, Y
通讯作者：
Kanayama, Y
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：
20.3
作者：
Jiang, F;Jia, YZ;Cohen, I
通讯作者：
Cohen, I
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA