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2015 ; 8
(ä): 101-9
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Generation of induced pluripotent stem cells from renal tubular cells of a
patient with Alport syndrome
#MMPMID26345127
Chen W
; Huang J
; Yu X
; Lin X
; Dai Y
Int J Nephrol Renovasc Dis
2015[]; 8
(ä): 101-9
PMID26345127
show ga
Alport syndrome (AS) is a hereditary disease that leads to kidney failure and is
caused by mutations in the COL4A3, COL4A4, and COL4A5 genes that lead to the
absence of collagen ?3?4?5 (IV) networks in the mature kidney glomerular basement
membrane. Approximately 80% of AS is X-linked because of mutations in COL4A5, the
gene encoding the alpha 5 chain of type IV collagen. To investigate the
pathogenesis of AS at the genetic level, we generated induced pluripotent stem
cells (iPSCs) from renal tubular cells of a patient with AS. The successful iPSC
generation laid the foundation to master the repair of the COL4A5 gene and to
evaluate the differentiation of iPSC into Sertoli cells and the accompanying
epigenetic changes at each stage. The generation of iPSCs from AS patients not
only confirms that iPSCs could be generated from renal tubular cells, but also
provides a novel type of genetic therapy for AS patients. In this study, we
generated iPSCs from renal tubular cells via ectopic expression of four
transcription factors (Oct4, Sox2, c-myc, and Klf4). According to the human
embryonic stem cell (hESC) charter, iPSC formation was confirmed by comparatively
analyzing hESC markers via colony morphology, immunohistochemistry, qRT-PCR, flow
cytometry, gene expression profiling of the three germ layers, and karyotyping.
Our results demonstrated that iPSCs were similar to hESCs with regard to
morphology, proliferation, hESC-specific surface marker expression, and
differentiation into the cell types of the three germ layers. The efficient
generation of iPSCs from the renal tubular cells of an AS patient would provide a
novel model to investigate the mechanisms underlying AS and to develop new
treatments for AS.