SOX9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys-Reference-Cited by-同舟云学术

SOX9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys

Published:2024-02-23 Issue:6685 Volume:383 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Aggarwal Shikhar¹²^ORCID,Wang Zhanxiang¹²^ORCID,Rincon Fernandez Pacheco David¹²^ORCID,Rinaldi Anna³^ORCID,Rajewski Alex⁴^ORCID,Callemeyn Jasper⁵^ORCID,Van Loon Elisabet⁵^ORCID,Lamarthée Baptiste⁵^ORCID,Covarrubias Ambart Ester⁶,Hou Jean⁷^ORCID,Yamashita Michifumi⁷^ORCID,Akiyama Haruhiko⁸^ORCID,Karumanchi S. Ananth²⁶^ORCID,Svendsen Clive N.¹²,Noble Paul W.⁹^ORCID,Jordan Stanley C.⁶,Breunig Joshua J.¹²^ORCID,Naesens Maarten⁵^ORCID,Cippà Pietro E.³¹⁰,Kumar Sanjeev¹²⁶^ORCID

Affiliation:

1. Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

2. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

3. Division of Nephrology, Ente Ospedaliero Cantonale, CH-6900 Lugano, Switzerland.

4. Applied Genomics, Computation, and Translational Core, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

5. Department of Microbiology, Immunology and Transplantation, KU Leuven, BE-3000 Leuven, Belgium.

6. Division of Nephrology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

7. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

8. Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.

9. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

10. Faculty of Biomedical Sciences, Università della Svizzera Italiana, CH-6900 Lugano, Switzerland.

Abstract

The steps governing healing with or without fibrosis within the same microenvironment are unclear. After acute kidney injury (AKI), injured proximal tubular epithelial cells activate SOX9 for self-restoration. Using a multimodal approach for a head-to-head comparison of injury-induced SOX9 lineages, we identified a dynamic SOX9 switch in repairing epithelia. Lineages that regenerated epithelia silenced SOX9 and healed without fibrosis (SOX9 on-off ). By contrast, lineages with unrestored apicobasal polarity maintained SOX9 activity in sustained efforts to regenerate, which were identified as a SOX9 on-on Cadherin6 pos cell state. These reprogrammed cells generated substantial single-cell WNT activity to provoke a fibroproliferative response in adjacent fibroblasts, driving AKI to chronic kidney disease. Transplanted human kidneys displayed similar SOX9/CDH6/WNT2B responses. Thus, we have uncovered a sensor of epithelial repair status, the activity of which determines regeneration with or without fibrosis.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.add6371

Reference69 articles.

1. Fibrosis — A Common Pathway to Organ Injury and Failure

2. Fibrosis: from mechanisms to medicines

3. Healing without scarring

4. Cellular and molecular pathways of renal repair after acute kidney injury

5. Molecular characterization of the transition from acute to chronic kidney injury following ischemia/reperfusion

Cited by 11 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. IL-4-induced SOX9 confers lineage plasticity to aged adult lung stem cells;Cell Reports;2024-08

2. Biology of the proximal tubule in body homeostasis and kidney disease;Nephrology Dialysis Transplantation;2024-07-26

3. Stepwise developmental mimicry generates proximal-biased kidney organoids;2024-07-02

4. Sox9 flips the switch between regeneration and fibrosis;Kidney International;2024-07

5. Animal models to study cognitive impairment of chronic kidney disease;American Journal of Physiology-Renal Physiology;2024-06-01