Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia
| Autor: | Karim Si-Tayeb, Salam Idriss, Benoite Champon, Amandine Caillaud, Matthieu Pichelin, Lucie Arnaud, Patricia Lemarchand, Cédric Le May, Kazem Zibara, Bertrand Cariou |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Disease Models & Mechanisms, Vol 9, Iss 1, Pp 81-90 (2016) |
| Druh dokumentu: | article |
| ISSN: | 1754-8411 1754-8403 |
| DOI: | 10.1242/dmm.022277 |
| Popis: | Proprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, PCSK9 loss-of-function (LOF) mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL). However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. We aimed to validate urine-sample-derived human induced pluripotent stem cells (UhiPSCs) as an appropriate tool to model PCSK9-mediated ADH and FHBL. To achieve our goal, urine-sample-derived somatic cells were reprogrammed into hiPSCs by using episomal vectors. UhiPSC were efficiently differentiated into hepatocyte-like cells (HLCs). Compared to control cells, cells originally derived from an individual with ADH (HLC-S127R) secreted less PCSK9 in the media (−38.5%; P=0.038) and had a 71% decrease (P |
| Databáze: | Directory of Open Access Journals |
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