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Single-cell profiling in COVID-19 associated acute kidney injury reveals patterns of tubule injury and repair in human
Preprint
in English
| bioRxiv
| ID: ppbiorxiv-463150
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A scientific journal published article is available and is probably based on this preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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A scientific journal published article is available and is probably based on this preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See journal article
ABSTRACT
The cellular mechanisms of kidney tubule repair are poorly characterized in human. Here, we applied single-nucleus RNA sequencing to analyze the kidney in the first days after acute injury in 5 critically ill patients with COVID-19. We identified abnormal proximal tubule cell states associated with injury, characterized by altered functional and metabolic profiles and by pro-fibrotic properties. Tubule repair involved the plasticity of mature tubule cells in a process of cell de-differentiation and re-differentiation, which displayed substantial similarities between mouse and man. In addition, in man we identified a peculiar tubule reparative response determining the expansion of progenitor-like cells marked by PROM1 and following a differentiation program characterized by the sequential activation of the WNT, NOTCH and HIPPO signaling pathways. Taken together, our analyses reveal cell state transitions and fundamental cellular hierarchies underlying kidney injury and repair in critically ill patients.
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Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Language:
English
Year:
2021
Document type:
Preprint