Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease
<p dir="ltr">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 unreso...
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2020
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| _version_ | 1864513511921549312 |
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| author | Gowher Ali (14152593) |
| author2 | Ahmed K. Elsayed (13275302) Manjula Nandakumar (1545811) Mohammed Bashir (5593550) Ihab Younis (57824) Yasmin Abu Aqel (18940657) Bushra Memon (4792767) Ramzi Temanni (671528) Fadhil Abubaker (14778163) Shahrad Taheri (57360) Essam M. Abdelalim (5768072) |
| author2_role | author author author author author author author author author author |
| author_facet | Gowher Ali (14152593) Ahmed K. Elsayed (13275302) Manjula Nandakumar (1545811) Mohammed Bashir (5593550) Ihab Younis (57824) Yasmin Abu Aqel (18940657) Bushra Memon (4792767) Ramzi Temanni (671528) Fadhil Abubaker (14778163) Shahrad Taheri (57360) Essam M. Abdelalim (5768072) |
| author_role | author |
| dc.creator.none.fl_str_mv | Gowher Ali (14152593) Ahmed K. Elsayed (13275302) Manjula Nandakumar (1545811) Mohammed Bashir (5593550) Ihab Younis (57824) Yasmin Abu Aqel (18940657) Bushra Memon (4792767) Ramzi Temanni (671528) Fadhil Abubaker (14778163) Shahrad Taheri (57360) Essam M. Abdelalim (5768072) |
| dc.date.none.fl_str_mv | 2020-04-02T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1089/scd.2019.0150 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Keratinocytes_Derived_from_Patient-Specific_Induced_Pluripotent_Stem_Cells_Recapitulate_the_Genetic_Signature_of_Psoriasis_Disease/26134075 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Psoriasis Keratinocytes (KCs) Genetic Signature Insulin Resistance Diabetes and Cardiovascular Diseases Pathogenesis RNA Sequencing |
| dc.title.none.fl_str_mv | Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Stem Cells and Development<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1089/scd.2019.0150" target="_blank">https://dx.doi.org/10.1089/scd.2019.0150</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_b721978ae329be65d98e8909ec6842e6 |
| identifier_str_mv | 10.1089/scd.2019.0150 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26134075 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis DiseaseGowher Ali (14152593)Ahmed K. Elsayed (13275302)Manjula Nandakumar (1545811)Mohammed Bashir (5593550)Ihab Younis (57824)Yasmin Abu Aqel (18940657)Bushra Memon (4792767)Ramzi Temanni (671528)Fadhil Abubaker (14778163)Shahrad Taheri (57360)Essam M. Abdelalim (5768072)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsPsoriasisKeratinocytes (KCs)Genetic SignatureInsulin ResistanceDiabetes and Cardiovascular DiseasesPathogenesisRNA Sequencing<p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Stem Cells and Development<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1089/scd.2019.0150" target="_blank">https://dx.doi.org/10.1089/scd.2019.0150</a></p>2020-04-02T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1089/scd.2019.0150https://figshare.com/articles/journal_contribution/Keratinocytes_Derived_from_Patient-Specific_Induced_Pluripotent_Stem_Cells_Recapitulate_the_Genetic_Signature_of_Psoriasis_Disease/26134075CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/261340752020-04-02T03:00:00Z |
| spellingShingle | Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease Gowher Ali (14152593) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Psoriasis Keratinocytes (KCs) Genetic Signature Insulin Resistance Diabetes and Cardiovascular Diseases Pathogenesis RNA Sequencing |
| status_str | publishedVersion |
| title | Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease |
| title_full | Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease |
| title_fullStr | Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease |
| title_full_unstemmed | Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease |
| title_short | Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease |
| title_sort | Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Psoriasis Keratinocytes (KCs) Genetic Signature Insulin Resistance Diabetes and Cardiovascular Diseases Pathogenesis RNA Sequencing |