Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiles of human iPSC derived podocytes

ABSTRACT: The gene expression profile of human iPSC derived podocytes were analyzed by utilizing NEPHS1-GFP knock-in human iPS cell line. The induced podocytes shows characteristic gene expression pattern that overlap with those of mouse and human podocytes in vivo. Kidney tissue was induced from human iPSC by our originally established protocol. NEPHS1-GPF knock-in human iPSC was used to isolate podocytes from induced kidney tissues. To identify the molecules which are specifically expressed in induced podocytes, NEPHS1-GFP positive and negative fractions were sorted by FACS and compared. RNA was isolated from cells and the gene expression profiles were determined by microarrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Atsuhiro Taguchi

PROVIDER: E-GEOD-66969 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Human Induced Pluripotent Stem Cell-Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation.

Sharmin Sazia S Taguchi Atsuhiro A Kaku Yusuke Y Yoshimura Yasuhiro Y Ohmori Tomoko T Sakuma Tetsushi T Mukoyama Masashi M Yamamoto Takashi T Kurihara Hidetake H Nishinakamura Ryuichi R

Journal of the American Society of Nephrology : JASN 20151119 6

Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator-like effector n ...[more]

PMID: 26586691

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Project description:We aimed to identify miRNA biomarkers of renal injury in kidney biopsies from patients with lupus nephritis. MiRNA profiles of 8 patients were analyzed for correlation with various clinical features including Progression, Activity, Chronicity, and Time to Kidney Failure. MicroRNAs (miRs) are promising biomarkers and are involved in pathogenesis of kidney diseases. We aimed to identify miR biomarkers of renal injury in kidney biopsies from patients with lupus nephritis and study their potential role in renal fibrosis. miR-150 was significantly increased in kidneys with high chronicity compared to low chronicity and it correlated positively with chronicity index scores and renal collagen I expression. In kidneys with high chronicity, miR-150 was found predominantly in proximal tubular cells (PTCs) and was moderately expressed in podocytes and to lesser degree in mesangial cells (MCs). We hypothesized that miR-150 increases fibrosis by downregulating a negative regulator of profibrotic proteins. Suppressor of cytokine signaling1 (SOCS1) is a predicted target of miR-150 and has shown antifibrotic role. After confirming that SOCS1 is a direct target of miR-150, we showed that transfection of a miR-150 analog downregulated SOCS1 protein and upregulated the profibrotic proteins fibronectin, collagen I, collagen III, and TGF-β1 in both primary normal human renal PTCs and MCs. A similar effect was seen when using a SOCS1 siRNA to confirm that the effect of miR-150 on profibrotic proteins is mediated through SOCS1. Stimulation with TGF-β1 induced miR-150 increase in PTCs and human podocytes but not MCs. These results suggest that miR-150 might be a useful quantitative renal biomarker of kidney injury in lupus nephritis and that miR-150, which might be partially induced by TGF-β1, plays an important role in renal fibrosis by increasing profibrotic molecules through downregulation of SOCS1. FFPE kidney specimens (n=25) including baseline and repeated needle renal biopsies were from 14 patients with LN enrolled in IRB-approved protocols at the NIDDK between 1976 and 1999. The specimens were divided in two groups based on histological chronicity index (CI). CI ≥ 4 were categorized as having high degree of chronicity of chronic kidney injury. 18 kidneys from 8 patients including high CI (n=9) and low CI (n=9) were used for miR profiling by Affymetrix microRNA microarrays.

Dataset Information

Gene expression profiles of human iPSC derived podocytes

Publications

Human Induced Pluripotent Stem Cell-Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation.

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