Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury.
Proc Natl Acad Sci U S A
; 117(27): 15874-15883, 2020 07 07.
Article
en En
| MEDLINE
| ID: mdl-32571916
ABSTRACT
After acute kidney injury (AKI), patients either recover or alternatively develop fibrosis and chronic kidney disease. Interactions between injured epithelia, stroma, and inflammatory cells determine whether kidneys repair or undergo fibrosis, but the molecular events that drive these processes are poorly understood. Here, we use single nucleus RNA sequencing of a mouse model of AKI to characterize cell states during repair from acute injury. We identify a distinct proinflammatory and profibrotic proximal tubule cell state that fails to repair. Deconvolution of bulk RNA-seq datasets indicates that this failed-repair proximal tubule cell (FR-PTC) state can be detected in other models of kidney injury, increasing during aging in rat kidney and over time in human kidney allografts. We also describe dynamic intercellular communication networks and discern transcriptional pathways driving successful vs. failed repair. Our study provides a detailed description of cellular responses after injury and suggests that the FR-PTC state may represent a therapeutic target to improve repair.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Lesión Renal Aguda
/
Transcriptoma
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Riñón
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Túbulos Renales Proximales
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2020
Tipo del documento:
Article