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Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression
by
Wu, Haojia
, Humphreys, Benjamin D.
, Karihaloo, Anil
, Muto, Yoshiharu
, Waikar, Sushrut S.
, Wilson, Parker C.
in
13
/ 38
/ 38/91
/ 45/62
/ 631/114/2114
/ 631/1647/514/1949
/ 631/208/212
/ 631/337/100/101
/ 692/699/1585
/ Accessibility
/ Binding sites
/ Chromatin
/ Chromatin - genetics
/ Diabetes
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 2 - complications
/ Diabetes Mellitus, Type 2 - genetics
/ Diabetes Mellitus, Type 2 - metabolism
/ Diabetic Nephropathies - genetics
/ Diabetic Nephropathies - metabolism
/ Diabetic nephropathy
/ Disease progression
/ External stimuli
/ Gene sequencing
/ Genetic Background
/ Glucocorticoids
/ Gluconeogenesis
/ Glucose
/ Glucose - metabolism
/ Humanities and Social Sciences
/ Humans
/ Inflammation
/ Injury prevention
/ Kidney diseases
/ Kidneys
/ Metabolism
/ multidisciplinary
/ Receptors
/ Receptors, Glucocorticoid - genetics
/ Science
/ Science (multidisciplinary)
/ Transcription factors
2022
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Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression
by
Wu, Haojia
, Humphreys, Benjamin D.
, Karihaloo, Anil
, Muto, Yoshiharu
, Waikar, Sushrut S.
, Wilson, Parker C.
in
13
/ 38
/ 38/91
/ 45/62
/ 631/114/2114
/ 631/1647/514/1949
/ 631/208/212
/ 631/337/100/101
/ 692/699/1585
/ Accessibility
/ Binding sites
/ Chromatin
/ Chromatin - genetics
/ Diabetes
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 2 - complications
/ Diabetes Mellitus, Type 2 - genetics
/ Diabetes Mellitus, Type 2 - metabolism
/ Diabetic Nephropathies - genetics
/ Diabetic Nephropathies - metabolism
/ Diabetic nephropathy
/ Disease progression
/ External stimuli
/ Gene sequencing
/ Genetic Background
/ Glucocorticoids
/ Gluconeogenesis
/ Glucose
/ Glucose - metabolism
/ Humanities and Social Sciences
/ Humans
/ Inflammation
/ Injury prevention
/ Kidney diseases
/ Kidneys
/ Metabolism
/ multidisciplinary
/ Receptors
/ Receptors, Glucocorticoid - genetics
/ Science
/ Science (multidisciplinary)
/ Transcription factors
2022
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Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression
by
Wu, Haojia
, Humphreys, Benjamin D.
, Karihaloo, Anil
, Muto, Yoshiharu
, Waikar, Sushrut S.
, Wilson, Parker C.
in
13
/ 38
/ 38/91
/ 45/62
/ 631/114/2114
/ 631/1647/514/1949
/ 631/208/212
/ 631/337/100/101
/ 692/699/1585
/ Accessibility
/ Binding sites
/ Chromatin
/ Chromatin - genetics
/ Diabetes
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 2 - complications
/ Diabetes Mellitus, Type 2 - genetics
/ Diabetes Mellitus, Type 2 - metabolism
/ Diabetic Nephropathies - genetics
/ Diabetic Nephropathies - metabolism
/ Diabetic nephropathy
/ Disease progression
/ External stimuli
/ Gene sequencing
/ Genetic Background
/ Glucocorticoids
/ Gluconeogenesis
/ Glucose
/ Glucose - metabolism
/ Humanities and Social Sciences
/ Humans
/ Inflammation
/ Injury prevention
/ Kidney diseases
/ Kidneys
/ Metabolism
/ multidisciplinary
/ Receptors
/ Receptors, Glucocorticoid - genetics
/ Science
/ Science (multidisciplinary)
/ Transcription factors
2022
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Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression
Journal Article
Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression
2022
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Overview
The proximal tubule is a key regulator of kidney function and glucose metabolism. Diabetic kidney disease leads to proximal tubule injury and changes in chromatin accessibility that modify the activity of transcription factors involved in glucose metabolism and inflammation. Here we use single nucleus RNA and ATAC sequencing to show that diabetic kidney disease leads to reduced accessibility of glucocorticoid receptor binding sites and an injury-associated expression signature in the proximal tubule. We hypothesize that chromatin accessibility is regulated by genetic background and closely-intertwined with metabolic memory, which pre-programs the proximal tubule to respond differently to external stimuli. Glucocorticoid excess has long been known to increase risk for type 2 diabetes, which raises the possibility that glucocorticoid receptor inhibition may mitigate the adverse metabolic effects of diabetic kidney disease.
Diabetic kidney disease leads to changes in glucose metabolism and inflammation. Here the authors use multimodal single cell sequencing to show that this disease leads to reduced accessibility of glucocorticoid receptor binding sites in the proximal tubule and increased gluconeogenesis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38
/ 38/91
/ 45/62
/ Diabetes
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 2 - complications
/ Diabetes Mellitus, Type 2 - genetics
/ Diabetes Mellitus, Type 2 - metabolism
/ Diabetic Nephropathies - genetics
/ Diabetic Nephropathies - metabolism
/ Glucose
/ Humanities and Social Sciences
/ Humans
/ Kidneys
/ Receptors, Glucocorticoid - genetics
/ Science
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