| Autor: |
Orlova, V.V., Nahon, D.M., Cochrane, A., Cao, X., Freund, C., Hil, F. van den, Westermann, C.J.J., Snijder, R.J., Amstel, J.K.P. van, Dijke, P. ten, Lebrin, F., Mager, H.J., Mummery, C.L. |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Stem Cell Reports, 17(7), 1536-1545. CELL PRESS |
| ISSN: |
2213-6711 |
| Popis: |
Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by weak blood vessels. HHT1 is caused by mutations in the ENDOGLIN (ENG) gene. Here, we generated induced pluripotent stem cells (hiPSCs) from a patient with rare mosaic HHT1 with tissues containing both mutant (ENG(c.)(1678C>)(T)) and normal cells, enabling derivation of isogenic diseased and healthy hiPSCs, respectively. We showed reduced ENG expression in HHT1 endothelial cells (HHT1-hiPSC-ECs), reflecting haploinsufficiency. HHT1(c.)(1678C)(>T)-hiPSC-ECs and the healthy isogenic control behaved similarly in two-dimensional (2D) culture, forming functionally indistinguishable vascular networks. However, when grown in 3D organ-on-chip devices under microfluidic flow, lumenized vessels formed in which defective vascular organization was evident: interaction between inner ECs and surrounding pericytes was decreased, and there was evidence for vascular leakage. Organs on chip thus revealed features of HHT in hiPSC-derived blood vessels that were not evident in conventional 2D assays. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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