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Disease modeling of ADAMTS9-related nephropathy using kidney organoids reveals its roles in tubular cells and podocytes
DC Field | Value | Language |
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dc.contributor.author | 김혜연 | - |
dc.contributor.author | 임정훈 | - |
dc.contributor.author | 지헌영 | - |
dc.date.accessioned | 2023-07-12T02:52:42Z | - |
dc.date.available | 2023-07-12T02:52:42Z | - |
dc.date.issued | 2023-03 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/195427 | - |
dc.description.abstract | Introduction: Mutations in ADAMTS9 cause nephronophthisis-related ciliopathies (NPHP-RC), which are characterized by multiple developmental defects and kidney diseases. Patients with NPHP-RC usually have normal glomeruli and negligible or no proteinuria. Herein, we identified novel compound-heterozygous ADAMTS9 variants in two siblings with NPHP-RC who had glomerular manifestations, including proteinuria. Methods: To investigate whether ADAMTS9 dysfunction causes NPHP and glomerulopathy, we differentiated ADAMTS9 knockout human induced pluripotent stem cells (hiPSCs) into kidney organoids. Single-cell RNA sequencing was utilized to elucidate the gene expression profiles from the ADAMTS9 knockout kidney organoids. Results: ADAMTS9 knockout had no effect on nephron differentiation; however, it reduced the number of primary cilia, thereby recapitulating renal ciliopathy. Single-cell transcriptomics revealed that podocyte clusters express the highest levels of ADAMTS9, followed by the proximal tubules. Loss of ADAMTS9 increased the activity of multiple signaling pathways, including the Wnt/PCP signaling pathway, in podocyte clusters. Conclusions: Mutations in ADMATS9 cause a glomerulotubular nephropathy in kidney and our study provides insights into the functional roles of ADMATS9 in glomeruli and tubules. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Frontiers Media S.A. | - |
dc.relation.isPartOf | FRONTIERS IN MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Disease modeling of ADAMTS9-related nephropathy using kidney organoids reveals its roles in tubular cells and podocytes | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pharmacology (약리학교실) | - |
dc.contributor.googleauthor | Seyoung Yu | - |
dc.contributor.googleauthor | Yo Jun Choi | - |
dc.contributor.googleauthor | John Hoon Rim | - |
dc.contributor.googleauthor | Hye-Youn Kim | - |
dc.contributor.googleauthor | Nasim Bekheirnia | - |
dc.contributor.googleauthor | Sarah Jane Swartz | - |
dc.contributor.googleauthor | Hongzheng Dai | - |
dc.contributor.googleauthor | Shen Linda Gu | - |
dc.contributor.googleauthor | Soyeon Lee | - |
dc.contributor.googleauthor | Ryuichi Nishinakamura | - |
dc.contributor.googleauthor | Friedhelm Hildebrandt | - |
dc.contributor.googleauthor | Mir Reza Bekheirnia | - |
dc.contributor.googleauthor | Heon Yung Gee | - |
dc.identifier.doi | 10.3389/fmed.2023.1089159 | - |
dc.contributor.localId | A05467 | - |
dc.contributor.localId | A04654 | - |
dc.contributor.localId | A03971 | - |
dc.relation.journalcode | J03762 | - |
dc.identifier.eissn | 2296-858X | - |
dc.identifier.pmid | 37035301 | - |
dc.subject.keyword | ADAMTS9 | - |
dc.subject.keyword | Nephronophthisis-related ciliopathy | - |
dc.subject.keyword | kidney organoid | - |
dc.subject.keyword | podocytes | - |
dc.subject.keyword | single-cell RNA sequencing | - |
dc.contributor.alternativeName | Kim, Hye-Youn | - |
dc.contributor.affiliatedAuthor | 김혜연 | - |
dc.contributor.affiliatedAuthor | 임정훈 | - |
dc.contributor.affiliatedAuthor | 지헌영 | - |
dc.citation.volume | 10 | - |
dc.citation.startPage | 1089159 | - |
dc.identifier.bibliographicCitation | FRONTIERS IN MEDICINE, Vol.10 : 1089159, 2023-03 | - |
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