Vitronectin-activated αvβ3 and αvβ5 integrin signalling specifies haematopoietic fate in human pluripotent stem cells
| Autor: | Tao Cheng, Jun Shen, Zicen Feng, Yaoyao Zhu, Shuzhen Lyu, Cuicui Lyu, Zack Z. Wang, Dixie L. Hoyle, Shuo Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pluripotent Stem Cells Mesoderm integrin Cellular differentiation extracellular matrix Integrin Original Manuscript Biology vitronectin Cell Line Extracellular matrix 03 medical and health sciences 0302 clinical medicine medicine Cell Adhesion Humans Receptors Vitronectin human pluripotent stem cells RNA Small Interfering Induced pluripotent stem cell Homeodomain Proteins Matrigel Cell Differentiation Cell Biology General Medicine Hematopoietic Stem Cells Integrin alphaVbeta3 Cell biology Haematopoiesis 030104 developmental biology medicine.anatomical_structure haematopoietic differentiation Gene Expression Regulation 030220 oncology & carcinogenesis biology.protein Vitronectin RNA Interference Signal Transduction Snake Venoms |
| Zdroj: | Cell Proliferation |
| ISSN: | 1365-2184 |
| Popis: | Objectives 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. Materials and Methods 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. Results 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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