Lima Cunha, Dulce ORCID: 0000-0002-6814-8365, Oram, Amanda, Gruber, Robert, Plank, Roswitha, Lingenhel, Arno, Gupta, Manoj K., Altmuller, Janine ORCID: 0000-0003-4372-1521, Nurnberg, Peter ORCID: 0000-0002-7228-428X, Schmuth, Matthias ORCID: 0000-0002-4064-1334, Zschocke, Johannes ORCID: 0000-0002-0046-8274, Saric, Tomo, Eckl, Katja M. and Hennies, Hans C. (2021). hiPSC-Derived Epidermal Keratinocytes from Ichthyosis Patients Show Altered Expression of Cornification Markers. Int. J. Mol. Sci., 22 (4). BASEL: MDPI. ISSN 1422-0067

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Abstract

Inherited ichthyoses represent a large heterogeneous group of skin disorders characterised by impaired epidermal barrier function and disturbed cornification. Current knowledge about disease mechanisms has been uncovered mainly through the use of mouse models or human skin organotypic models. However, most mouse lines suffer from severe epidermal barrier defects causing neonatal death and human keratinocytes have very limited proliferation ability in vitro. Therefore, the development of disease models based on patient derived human induced pluripotent stem cells (hiPSCs) is highly relevant. For this purpose, we have generated hiPSCs from patients with congenital ichthyosis, either non-syndromic autosomal recessive congenital ichthyosis (ARCI) or the ichthyosis syndrome trichothiodystrophy (TTD). hiPSCs were successfully differentiated into basal keratinocyte-like cells (hiPSC-bKs), with high expression of epidermal keratins. In the presence of higher calcium concentrations, terminal differentiation of hiPSC-bKs was induced and markers KRT1 and IVL expressed. TTD1 hiPSC-bKs showed reduced expression of FLG, SPRR2B and lipoxygenase genes. ARCI hiPSC-bKs showed more severe defects, with downregulation of several cornification genes. The application of hiPSC technology to TTD1 and ARCI demonstrates the successful generation of in vitro models mimicking the disease phenotypes, proving a valuable system both for further molecular investigations and drug development for ichthyosis patients.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lima Cunha, DulceUNSPECIFIEDorcid.org/0000-0002-6814-8365UNSPECIFIED
Oram, AmandaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruber, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plank, RoswithaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lingenhel, ArnoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gupta, Manoj K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmuller, JanineUNSPECIFIEDorcid.org/0000-0003-4372-1521UNSPECIFIED
Nurnberg, PeterUNSPECIFIEDorcid.org/0000-0002-7228-428XUNSPECIFIED
Schmuth, MatthiasUNSPECIFIEDorcid.org/0000-0002-4064-1334UNSPECIFIED
Zschocke, JohannesUNSPECIFIEDorcid.org/0000-0002-0046-8274UNSPECIFIED
Saric, TomoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckl, Katja M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hennies, Hans C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-593673
DOI: 10.3390/ijms22041785
Journal or Publication Title: Int. J. Mol. Sci.
Volume: 22
Number: 4
Date: 2021
Publisher: MDPI
Place of Publication: BASEL
ISSN: 1422-0067
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Biochemistry & Molecular Biology; Chemistry, MultidisciplinaryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59367

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