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Single-cell RNA sequencing reveals renal endothelium heterogeneity and metabolic adaptation to water deprivation
- Source :
- J Am Soc Nephrol, Journal of the American Society of Nephrology, Dumas, S J, Meta, E, Borri, M, Goveia, J, Rohlenova, K, Conchinha, N V, Falkenberg, K, Teuwen, L-A, de Rooij, L, Kalucka, J, Chen, R, Khan, S, Taverna, F, Lu, W, Parys, M, De Legher, C, Vinckier, S, Karakach, T K, Schoonjans, L, Lin, L, Bolund, L, Dewerchin, M, Eelen, G, Rabelink, T J, Li, X, Luo, Y & Carmeliet, P 2020, ' Single-Cell RNA Sequencing Reveals Renal Endothelium Heterogeneity and Metabolic Adaptation to Water Deprivation ', Journal of the American Society of Nephrology : JASN, vol. 31, no. 1, pp. 118-138 . https://doi.org/10.1681/ASN.2019080832, Journal of the American Society of Nephrology, 31(1), 118-138. AMER SOC NEPHROLOGY
- Publication Year :
- 2020
-
Abstract
- BACKGROUND: Renal endothelial cells from glomerular, cortical, and medullary kidney compartments are exposed to different microenvironmental conditions and support specific kidney processes. However, the heterogeneous phenotypes of these cells remain incompletely inventoried. Osmotic homeostasis is vitally important for regulating cell volume and function, and in mammals, osmotic equilibrium is regulated through the countercurrent system in the renal medulla, where water exchange through endothelium occurs against an osmotic pressure gradient. Dehydration exposes medullary renal endothelial cells to extreme hyperosmolarity, and how these cells adapt to and survive in this hypertonic milieu is unknown. METHODS: We inventoried renal endothelial cell heterogeneity by single-cell RNA sequencing >40,000 mouse renal endothelial cells, and studied transcriptome changes during osmotic adaptation upon water deprivation. We validated our findings by immunostaining and functionally by targeting oxidative phosphorylation in a hyperosmolarity model in vitro and in dehydrated mice in vivo. RESULTS: We identified 24 renal endothelial cell phenotypes (of which eight were novel), highlighting extensive heterogeneity of these cells between and within the cortex, glomeruli, and medulla. In response to dehydration and hypertonicity, medullary renal endothelial cells upregulated the expression of genes involved in the hypoxia response, glycolysis, and-surprisingly-oxidative phosphorylation. Endothelial cells increased oxygen consumption when exposed to hyperosmolarity, whereas blocking oxidative phosphorylation compromised endothelial cell viability during hyperosmotic stress and impaired urine concentration during dehydration. CONCLUSIONS: This study provides a high-resolution atlas of the renal endothelium and highlights extensive renal endothelial cell phenotypic heterogeneity, as well as a previously unrecognized role of oxidative phosphorylation in the metabolic adaptation of medullary renal endothelial cells to water deprivation. ispartof: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY vol:31 issue:1 pages:118-138 ispartof: location:United States status: published
- Subjects :
- 0301 basic medicine
Male
Kidney
Transcriptome
Mice
0302 clinical medicine
AMINO-ACIDS
OSMOLYTES
GENE-EXPRESSION
Dehydration
Chemistry
urine concentration
renal endothelial cells
General Medicine
Adaptation, Physiological
Cell biology
Endothelial stem cell
scRNA-sequencing
medicine.anatomical_structure
Phenotype
Nephrology
Osmotic shock
Endothelium
METFORMIN
Energy metabolism
oxidative phosphorylation
MECHANISMS
03 medical and health sciences
KIDNEY
medicine
Renal medulla
Animals
Humans
IDENTIFICATION
Osmotic concentration
Water Deprivation
business.industry
Sequence Analysis, RNA
Endothelial Cells
dehydration
medicine.disease
Mice, Inbred C57BL
030104 developmental biology
Basic Research
VOLUME
INFERENCE
heterogeneity
business
030217 neurology & neurosurgery
Homeostasis
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- J Am Soc Nephrol, Journal of the American Society of Nephrology, Dumas, S J, Meta, E, Borri, M, Goveia, J, Rohlenova, K, Conchinha, N V, Falkenberg, K, Teuwen, L-A, de Rooij, L, Kalucka, J, Chen, R, Khan, S, Taverna, F, Lu, W, Parys, M, De Legher, C, Vinckier, S, Karakach, T K, Schoonjans, L, Lin, L, Bolund, L, Dewerchin, M, Eelen, G, Rabelink, T J, Li, X, Luo, Y & Carmeliet, P 2020, ' Single-Cell RNA Sequencing Reveals Renal Endothelium Heterogeneity and Metabolic Adaptation to Water Deprivation ', Journal of the American Society of Nephrology : JASN, vol. 31, no. 1, pp. 118-138 . https://doi.org/10.1681/ASN.2019080832, Journal of the American Society of Nephrology, 31(1), 118-138. AMER SOC NEPHROLOGY
- Accession number :
- edsair.doi.dedup.....8b0e38fe50f3082bab431c22dbafebb4