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

Ali, Gowher; Elsayed, Ahmed K.; Nandakumar, Manjula; Bashir, Mohammed; Younis, Ihab; Aqel, Yasmin Abu; Memon, Bushra; Temanni, Ramzi; Abubaker, Fadhil; Taheri, Shahrad; Abdelalim, Essam M.

doi:10.1089/scd.2019.0150

Cited by 37 publications

(42 citation statements)

References 78 publications

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“…Recently, we reported the generation of an iPSC line from a patient with a heterozygous deletion in FOXA2 gene (QBRIi009-A; FOXA2 +/− iPSC-C1) 24 and from a healthy control (QBRIi001; Ctr1-iPSCs) 25 . In this study, we generated additional iPSC lines from another healthy control (Ctr2-iPSCs).…”

Section: Resultsmentioning

confidence: 99%

“…Immunostaining and flow cytometry were performed as previously reported 27 , 29 . RT-PCR and qPCR were performed as previously reported 25 . (The antibody and primer details are listed in protocol was used in Supplementary Tables S2 and S3 .)…”

Section: Methodsmentioning

confidence: 99%

“…The RNA-Sequencing (RNA-Seq) experiments and data analysis were performed as we previously reported 25 , 47 . For the analysis, the RNA-Seq data were pooled from two Ctr-iPSC lines and three FOXA2 +/− iPSC lines of two independent experiments.…”

Section: Methodsmentioning

confidence: 99%

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Aberrant development of pancreatic beta cells derived from human iPSCs with FOXA2 deficiency

et al. 2021

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FOXA2 has been identified as an essential factor for pancreas development and emerging evidence supports an association between FOXA2 and diabetes. Although the role of FOXA2 during pancreatic development is well-studied in animal models, its role during human islet cell development remains unclear. Here, we generated induced pluripotent stem cells (iPSCs) from a patient with FOXA2 haploinsufficiency (FOXA2+/− iPSCs) followed by beta-cell differentiation to understand the role of FOXA2 during pancreatic beta-cell development. Our results showed that FOXA2 haploinsufficiency resulted in aberrant expression of genes essential for the differentiation and proper functioning of beta cells. At pancreatic progenitor (PP2) and endocrine progenitor (EPs) stages, transcriptome analysis showed downregulation in genes associated with pancreatic development and diabetes and upregulation in genes associated with nervous system development and WNT signaling pathway. Knockout of FOXA2 in control iPSCs (FOXA2−/− iPSCs) led to severe phenotypes in EPs and beta-cell stages. The expression of NGN3 and its downstream targets at EPs as well as INSUILIN and GLUCAGON at the beta-cell stage, were almost absent in the cells derived from FOXA2−/− iPSCs. These findings indicate that FOXA2 is crucial for human pancreatic endocrine development and its defect may lead to diabetes based on FOXA2 dosage.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Aberrant development of pancreatic beta cells derived from human iPSCs with FOXA2 deficiency

et al. 2021

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“…In 2012, Tsoi et al demonstrated a list of notable genes from the newly identified psoriasis loci and one of them was KLF4 (9p.31.2) [13]. Recently, in 2020, an upregulation of the KLF4 gene in psoriatic keratinocytes has been proved [14]. Therefore the studies cited encourage to deepen research on KLF4 in psoriasis.…”

Section: Introductionmentioning

confidence: 99%

Elevated circulating Krüppel-like factor 4 level as a novel independent marker of the proatherogenic risk in patients with psoriasis: a preliminary study

Baran¹,

Krahel²,

Kamiński³

et al. 2021

pdia

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Introduction: Krüppel-like factor 4 (KLF4) is a transcription factor of anti-inflammatory and anti-thrombotic properties not studied in psoriasis yet. Aim: To analyze the clinical value of the serum KLF4 level in psoriatics and elucidate the interplay between disease activity, metabolic or inflammatory parameters and systemic therapy. Material and methods: The study enrolled thirty-four psoriatics and fifteen healthy subjects. Blood samples were collected before and after twelve weeks of treatment with methotrexate or acitretin. Serum KLF4 levels were measured using immune-enzymatic method. Results: Serum KLF4 levels in psoriatic patients did not statistically differ comparing to the controls (p > 0.05). However, in severe psoriasis, KLF4 was significantly higher than in healthy ones before treatment and normalized after treatment to baseline levels of controls (p < 0.05, p > 0.05, respectively). KLF4 positively correlated with body mass index (p = 0.038) but not with psoriasis severity, nor inflammatory or metabolic markers. Interestingly, many pro-atherogenic parameters were shown as variables independently predicting the levels of KLF4. No significant effect of three-month systemic treatment on KLF4 was found. Conclusions: KLF4 may be a novel independent indicator of the proatherogenic risk in psoriatics, especially with a severe form or obesity.

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“…Real time RT-PCR analysis was performed using GoTaq qPCR Master Mix (Promega) as previously described [20]. The primer details are listed in Table S2.…”

Section: Real Time Pcr Analysismentioning

confidence: 99%

Scalable Generation of Mesenchymal Stem Cells and Adipocytes from Human Pluripotent Stem Cells

Karam

Younis

Elareer

et al. 2020

Cells

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Human pluripotent stem cells (hPSCs) can provide unlimited supply for mesenchymal stem cells (MSCs) and adipocytes that can be used for therapeutic applications. Here we developed a simple and highly efficient all-trans-retinoic acid (RA)-based method for generating an off-the-shelf and scalable number of human pluripotent stem cell (hPSC)-derived MSCs with enhanced adipogenic potential. We showed that short exposure of multiple hPSC lines (hESCs/hiPSCs) to 10 µM RA dramatically enhances embryoid body (EB) formation through regulation of genes activating signaling pathways associated with cell proliferation, survival and adhesion, among others. Disruption of cell adhesion induced the subsequent differentiation of the highly expanded RA-derived EB-forming cells into a pure population of multipotent MSCs (up to 1542-fold increase in comparison to RA-untreated counterparts). Interestingly, the RA-derived MSCs displayed enhanced differentiation potential into adipocytes. Thus, these findings present a novel RA-based approach for providing an unlimited source of MSCs and adipocytes that can be used for regenerative medicine, drug screening and disease modeling applications.

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

Cited by 37 publications

References 78 publications

Aberrant development of pancreatic beta cells derived from human iPSCs with FOXA2 deficiency

Aberrant development of pancreatic beta cells derived from human iPSCs with FOXA2 deficiency

Elevated circulating Krüppel-like factor 4 level as a novel independent marker of the proatherogenic risk in patients with psoriasis: a preliminary study

Scalable Generation of Mesenchymal Stem Cells and Adipocytes from Human Pluripotent Stem Cells

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