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Single-cell profiling in COVID-19 associated acute kidney injury reveals patterns of tubule injury and repair in human
David Legouis; Anna Rinaldi; Gregoire Arnoux; Thomas Verissimo; Jennifer Scotti-Gerber; Anna Faivre; Manuel Schibler; Andrea Rinaldi; Maarten Naesens; Kari Koppitch; Jérôme Pugin; Andrew P McMahon; Solange Moll; Sophie de Seigneux; Pietro E Cippà.
Affiliation
  • David Legouis; Geneva University Hospitals
  • Anna Rinaldi; Ente Ospedaliero Cantonale
  • Gregoire Arnoux; University Hospital of Geneva
  • Thomas Verissimo; University of Geneva
  • Jennifer Scotti-Gerber; Ente Ospedaliero Cantonale
  • Anna Faivre; University of Geneva
  • Manuel Schibler; University of Geneva Hospitals
  • Andrea Rinaldi; Institute of Oncological Research
  • Maarten Naesens; University Hospitals Leuven
  • Kari Koppitch; University of Southern California,
  • Jérôme Pugin; University Hospital of Geneva
  • Andrew P McMahon; University of Southern California,
  • Solange Moll; University Hospital of Geneva
  • Sophie de Seigneux; University Hospital of Geneva
  • Pietro E Cippà; Ente Ospedaliero Cantonale
Preprint in English | bioRxiv | ID: ppbiorxiv-463150
Journal article
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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.
License
cc_by_nc_nd
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
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