TY - JOUR
T1 - Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease
AU - Ali, Gowher
AU - Elsayed, Ahmed K.
AU - Nandakumar, Manjula
AU - Bashir, Mohammed
AU - Younis, Ihab
AU - Abu Aqel, Yasmin
AU - Memon, Bushra
AU - Temanni, Ramzi
AU - Abubaker, Fadhil
AU - Taheri, Shahrad
AU - Abdelalim, Essam M.
N1 - Publisher Copyright:
© Gowher Ali et al. 2020; Published by Mary Ann Liebert, Inc. 2020.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - genetic predisposition
KW - induced pluripotent stem cells
KW - insulin resistance
KW - keratinocytes
KW - skin disorder
KW - transcriptome profiling
UR - http://www.scopus.com/inward/record.url?scp=85083078253&partnerID=8YFLogxK
U2 - 10.1089/scd.2019.0150
DO - 10.1089/scd.2019.0150
M3 - Article
C2 - 31996098
AN - SCOPUS:85083078253
SN - 1547-3287
VL - 29
SP - 383
EP - 400
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 7
ER -