IPSC-induced podocytes from a BORS patient with EYA1 gene mutation showed glucocorticoid-resistant and cytoskeletal rearrangement
Abstract The primary cause of branchio-oto-renal syndrome (BORS) is mutations in the EYA1 gene. The aim of this study was to investigate the clinical characteristics associated with induced podocyte reappearance in children with BORS and EYA1 mutations. We collected clinical and genetic data...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-06-01
|
| Series: | Cellular and Molecular Life Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s00018-025-05724-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849237648137256960 |
|---|---|
| author | Guanyu Li Di Lu Liujing Xu Shumin Zhou Jiayi Zhang Lijuan Wu Lingna Shi Lili Wang Xiaoqing Lin Zhigang Ma Ming Liu Xia Gao |
| author_facet | Guanyu Li Di Lu Liujing Xu Shumin Zhou Jiayi Zhang Lijuan Wu Lingna Shi Lili Wang Xiaoqing Lin Zhigang Ma Ming Liu Xia Gao |
| author_sort | Guanyu Li |
| collection | DOAJ |
| description | Abstract The primary cause of branchio-oto-renal syndrome (BORS) is mutations in the EYA1 gene. The aim of this study was to investigate the clinical characteristics associated with induced podocyte reappearance in children with BORS and EYA1 mutations. We collected clinical and genetic data from a 4-year-old girl diagnosed with BORS and her family. Induced pluripotent stem cells (iPSC) were derived from peripheral blood mononuclear cells of both the patient and healthy individuals, which were differentiated into podocytes in vitro. RNA-seq was used to analyze differentially expressed genes in both groups. Here, the proband, along with his brother and mother, exhibited symptoms of BORS. WES analysis identified a heterozygous splicing variant at the EYA1 locus: c.1050 + 5G > A, inherited from his mother. The proband was initially glucocorticoid-resistant. After tacrolimus treatment, his urine protein/creatinine ratio significantly improved. Compared to healthy individuals, patient-derived podocytes displayed increased motility and pronounced cytoskeletal rearrangement. RNA-Seq results indicated significant downregulation of cell adhesion molecule and cytoskeletal rearrangement signaling pathway expression in patient-derived podocytes. Dexamethasone was ineffective in ameliorating the pathological damage induced by puromycin aminonucleoside in patient-derived podocytes. In BORS patients, podocytes exhibit cytoskeletal reorganization and enhanced motility in vitro while showing resistance to steroid treatment. These findings were consistent with the clinical features observed in the patient, suggesting that this unique cellular disease model merits further investigation. |
| format | Article |
| id | doaj-art-e58e8f4573fe41bf928e7434030531c6 |
| institution | Kabale University |
| issn | 1420-9071 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Cellular and Molecular Life Sciences |
| spelling | doaj-art-e58e8f4573fe41bf928e7434030531c62025-08-20T04:01:53ZengSpringerCellular and Molecular Life Sciences1420-90712025-06-0182111610.1007/s00018-025-05724-7IPSC-induced podocytes from a BORS patient with EYA1 gene mutation showed glucocorticoid-resistant and cytoskeletal rearrangementGuanyu Li0Di Lu1Liujing Xu2Shumin Zhou3Jiayi Zhang4Lijuan Wu5Lingna Shi6Lili Wang7Xiaoqing Lin8Zhigang Ma9Ming Liu10Xia Gao11Nephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityPediatrics, Gansu Provincial HospitalDepartment of Radiology, Gansu Provincial HospitalNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityNephrology Department, Longgang District People’s Hospital of ShenzhenGuangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityNephrology Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityAbstract The primary cause of branchio-oto-renal syndrome (BORS) is mutations in the EYA1 gene. The aim of this study was to investigate the clinical characteristics associated with induced podocyte reappearance in children with BORS and EYA1 mutations. We collected clinical and genetic data from a 4-year-old girl diagnosed with BORS and her family. Induced pluripotent stem cells (iPSC) were derived from peripheral blood mononuclear cells of both the patient and healthy individuals, which were differentiated into podocytes in vitro. RNA-seq was used to analyze differentially expressed genes in both groups. Here, the proband, along with his brother and mother, exhibited symptoms of BORS. WES analysis identified a heterozygous splicing variant at the EYA1 locus: c.1050 + 5G > A, inherited from his mother. The proband was initially glucocorticoid-resistant. After tacrolimus treatment, his urine protein/creatinine ratio significantly improved. Compared to healthy individuals, patient-derived podocytes displayed increased motility and pronounced cytoskeletal rearrangement. RNA-Seq results indicated significant downregulation of cell adhesion molecule and cytoskeletal rearrangement signaling pathway expression in patient-derived podocytes. Dexamethasone was ineffective in ameliorating the pathological damage induced by puromycin aminonucleoside in patient-derived podocytes. In BORS patients, podocytes exhibit cytoskeletal reorganization and enhanced motility in vitro while showing resistance to steroid treatment. These findings were consistent with the clinical features observed in the patient, suggesting that this unique cellular disease model merits further investigation.https://doi.org/10.1007/s00018-025-05724-7Branchio-oto-renal syndromeInduced pluripotent stem cellsPodocytes |
| spellingShingle | Guanyu Li Di Lu Liujing Xu Shumin Zhou Jiayi Zhang Lijuan Wu Lingna Shi Lili Wang Xiaoqing Lin Zhigang Ma Ming Liu Xia Gao IPSC-induced podocytes from a BORS patient with EYA1 gene mutation showed glucocorticoid-resistant and cytoskeletal rearrangement Cellular and Molecular Life Sciences Branchio-oto-renal syndrome Induced pluripotent stem cells Podocytes |
| title | IPSC-induced podocytes from a BORS patient with EYA1 gene mutation showed glucocorticoid-resistant and cytoskeletal rearrangement |
| title_full | IPSC-induced podocytes from a BORS patient with EYA1 gene mutation showed glucocorticoid-resistant and cytoskeletal rearrangement |
| title_fullStr | IPSC-induced podocytes from a BORS patient with EYA1 gene mutation showed glucocorticoid-resistant and cytoskeletal rearrangement |
| title_full_unstemmed | IPSC-induced podocytes from a BORS patient with EYA1 gene mutation showed glucocorticoid-resistant and cytoskeletal rearrangement |
| title_short | IPSC-induced podocytes from a BORS patient with EYA1 gene mutation showed glucocorticoid-resistant and cytoskeletal rearrangement |
| title_sort | ipsc induced podocytes from a bors patient with eya1 gene mutation showed glucocorticoid resistant and cytoskeletal rearrangement |
| topic | Branchio-oto-renal syndrome Induced pluripotent stem cells Podocytes |
| url | https://doi.org/10.1007/s00018-025-05724-7 |
| work_keys_str_mv | AT guanyuli ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT dilu ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT liujingxu ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT shuminzhou ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT jiayizhang ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT lijuanwu ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT lingnashi ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT liliwang ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT xiaoqinglin ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT zhigangma ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT mingliu ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement AT xiagao ipscinducedpodocytesfromaborspatientwitheya1genemutationshowedglucocorticoidresistantandcytoskeletalrearrangement |