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03554nam a2200709Ia 4500 |
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10-1016-j-ajpath-2021-11-004 |
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220420s2022 CNT 000 0 und d |
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|a 00029440 (ISSN)
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| 245 |
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|a Single-Cell Transcriptomics Reveal Disrupted Kidney Filter Cell-Cell Interactions after Early and Selective Podocyte Injury
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|b Elsevier Inc.
|c 2022
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|a 14
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|z View Fulltext in Publisher
|u https://doi.org/10.1016/j.ajpath.2021.11.004
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|a The health of the kidney filtration barrier requires communication among podocytes, endothelial cells, and mesangial cells. Disruption of these cell-cell interactions is thought to contribute to disease progression in chronic kidney diseases (CKDs). Podocyte ablation via doxycycline-inducible deletion of an essential endogenous molecule, CTCF [inducible podocyte-specific CTCF deletion (iCTCFpod−/−)], is sufficient to drive progressive CKD. However, the earliest events connecting podocyte injury to disrupted intercellular communication within the kidney filter remain unclear. Single-cell RNA sequencing of kidney tissue from iCTCFpod−/− mice after 1 week of doxycycline induction was performed to generate a map of the earliest transcriptional effects of podocyte injury on cell-cell interactions at single-cell resolution. A subset of podocytes had the earliest signs of injury due to disrupted gene programs for cytoskeletal regulation and mitochondrial function. Surviving podocytes up-regulated collagen type IV ɑ5, causing reactive changes in integrin expression in endothelial populations and mesangial cells. Intercellular interaction analysis revealed several receptor-ligand-target gene programs as drivers of endothelial cell injury and abnormal matrix deposition. This analysis reveals the earliest disruptive changes within the kidney filter, pointing to new, actionable targets within a therapeutic window that may allow us to maximize the success of much needed therapeutic interventions for CKDs. © 2022 American Society for Investigative Pathology
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|a animal
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|a animal cell
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|a Animals
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|a Article
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|a cell communication
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|a Cell Communication
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|a cell damage
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|a cell interaction
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|a cell population
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|a cell survival
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|a chronic kidney failure
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|a collagen type 4
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|a controlled study
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|a cytoskeleton
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|a female
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|a genetics
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|a glomerulus filtration
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|a integrin
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|a knockout mouse
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|a male
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|a mesangium cell
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|a metabolism
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|a Mice
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|a Mice, Knockout
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|a mitochondrion
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|a mouse
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|a nonhuman
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|a pathology
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|a podocyte
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|a Podocytes
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|a protein expression
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|a Renal Insufficiency, Chronic
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| 650 |
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|a RNA sequencing
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|a signal transduction
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| 650 |
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|a single cell analysis
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|a Single-Cell Analysis
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|a transcriptome
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|a Transcriptome
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|a transcriptomics
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|a upregulation
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| 700 |
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|a Chen, F.
|e author
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|a Chen, H.
|e author
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|a Clark, A.R.
|e author
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|a Greka, A.
|e author
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|a Marshall, J.
|e author
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|a Montesinos, M.S.
|e author
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|a Nguyen, L.
|e author
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|a Zhou, Y.
|e author
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| 773 |
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|t American Journal of Pathology
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