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Epigenetic reprogramming driving successful and failed repair in acute kidney injury.
Muto, Yoshiharu; Dixon, Eryn E; Yoshimura, Yasuhiro; Ledru, Nicolas; Kirita, Yuhei; Wu, Haojia; Humphreys, Benjamin D.
Afiliação
  • Muto Y; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Dixon EE; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Yoshimura Y; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Ledru N; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Kirita Y; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Wu H; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Humphreys BD; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Sci Adv ; 10(32): eado2849, 2024 Aug 09.
Article em En | MEDLINE | ID: mdl-39110788
ABSTRACT
Acute kidney injury (AKI) causes epithelial damage followed by subsequent repair. While successful repair restores kidney function, this process is often incomplete and can lead to chronic kidney disease (CKD) in a process called failed repair. To better understand the epigenetic reprogramming driving this AKI-to-CKD transition, we generated a single-nucleus multiomic atlas for the full mouse AKI time course, consisting of ~280,000 single-nucleus transcriptomes and epigenomes. We reveal cell-specific dynamic alterations in gene regulatory landscapes reflecting, especially, activation of proinflammatory pathways. We further generated single-nucleus multiomic data from four human AKI samples including validation by genome-wide identification of nuclear factor κB binding sites. A regularized regression analysis identifies key regulators involved in both successful and failed repair cell fate, identifying the transcription factor CREB5 as a regulator of both successful and failed tubular repair that also drives proximal tubular cell proliferation after injury. Our interspecies multiomic approach provides a foundation to comprehensively understand cell states in AKI.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Epigênese Genética / Injúria Renal Aguda Limite: Animals / Humans Idioma: En Revista: Sci Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Epigênese Genética / Injúria Renal Aguda Limite: Animals / Humans Idioma: En Revista: Sci Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos