Manara - Qatar Research Repository
Browse
1/1
2 files

Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease

journal contribution
submitted on 2024-07-01, 12:04 and posted on 2024-07-01, 12:19 authored by Gowher Ali, Ahmed K. Elsayed, Manjula Nandakumar, Mohammed Bashir, Ihab Younis, Yasmin Abu Aqel, Bushra Memon, Ramzi Temanni, Fadhil Abubaker, Shahrad Taheri, Essam M. Abdelalim

Psoriasis is characterized by hyperproliferation and defective differentiation of keratinocytes (KCs). Patients with psoriasis are at a high risk of developing diabetes and cardiovascular diseases. The debate on the genetic origin of psoriasis pathogenesis remains unresolved due to lack of suitable in vitro human models mimicking the disease phenotypes. In this study, we provide the first human induced pluripotent stem cell (iPSC) model for psoriasis carrying the genetic signature of the patients. iPSCs were generated from patients with psoriasis (PsO-iPSCs) and healthy donors (Ctr-iPSCs) and were efficiently differentiated into mature KCs. RNA sequencing of KCs derived from Ctr-iPSCs and PsO-iPSCs identified 361 commonly upregulated and 412 commonly downregulated genes. KCs derived from PsO-iPSCs showed dysregulated transcripts associated with psoriasis and KC differentiation, such as HLA-C, KLF4, chemokines, type I interferon-inducible genes, solute carrier family, IVL, DSG1, and HLA-DQA1, as well as transcripts associated with insulin resistance, such as IRS2, GDF15, GLUT10, and GLUT14. Our data suggest that the KC abnormalities are the main driver triggering psoriasis pathology and highlights the substantial contribution of genetic predisposition in the development of psoriasis and insulin resistance.

Other Information

Published in: Stem Cells and Development
License: https://creativecommons.org/licenses/by/4.0
See article on publisher's website: https://dx.doi.org/10.1089/scd.2019.0150

Funding

Open Access funding provided by Hamad Bin Khalifa University, Qatar Biomedical Research Institute.

History

Language

  • English

Publisher

Mary Ann Liebert

Publication Year

  • 2020

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute - HBKU
  • College of Health and Life Sciences - HBKU
  • Hamad Medical Corporation
  • Qatar Metabolic Institute - HMC
  • Carnegie Mellon University in Qatar
  • Sidra Medicine
  • Weill Cornell Medicine - Qatar