Dataset Information


Global gene expression in patient keratinocytes and patient-specific iPS-derived keratinocytes

ABSTRACT: Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional Type VII collagen and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma (SCC). The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We have formed a multidisciplinary team with the ultimate goal to develop an iPSC-based therapy for RDEB. Here, we present a clinical protocol that generates autologous, corrected epithelial keratinocyte sheets with the COL7A1 gene mutation corrected for grafting on to patients. We demonstrate the utility of sequential reprogramming and novel adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity and secreted wild-type collagen VII, resulting in stratified epidermis in vitro and in vivo in mice. Sequencing of corrected cell lines prior to tissue formation revealed heterogeneity of SCC-predisposing mutations, allowing us to select COL7A1 corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a first clinical platform to use iPSCs in the treatment of debilitating genodermatoses. Microarray analysis of iPS-derived keratinocytes from two RDEB patients (iPS-K1 and iPS-K3), corresponding patient keratinocytes (AHK1 and AHK2), normal human keratinocytes (NHK), as well as H9 human embryonic stem cells (hESC - H9). All samples were analyzed in duplicate and differential gene expression was measured relative to H9.

ORGANISM(S): Homo sapiens  

SUBMITTER: John Hawkins  Marius Wernig   Sandra Melo   Zurab Siprashvili   Seung K Kim   Pei Wang   Alfred T Lane   Susie Lee   Jiang Li   Gerhard Bauer   Anthony E Oro   Leszek Lisowski   Lisa Bashkirova   Mohammed Ameen   Lingjie Li   Mark A Kay   Aaron Schwertschkow   Bahareh H Derafshi   Hanson H Zhen   Vittorio Sebastiano   Anthony Oro   Andrea Tichy   Thomas Leung    

PROVIDER: E-GEOD-63101 | ArrayExpress | 2014-11-28



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