A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys.
Blue B LakeSong ChenMasato HoshiNongluk PlongthongkumDiane SalamonAmanda KnotenAnitha VijayanRamakrishna VenkateshEric H KimDerek GaoJoseph GautKun ZhangSanjay JainPublished in: Nature communications (2019)
Defining cellular and molecular identities within the kidney is necessary to understand its organization and function in health and disease. Here we demonstrate a reproducible method with minimal artifacts for single-nucleus Droplet-based RNA sequencing (snDrop-Seq) that we use to resolve thirty distinct cell populations in human adult kidney. We define molecular transition states along more than ten nephron segments spanning two major kidney regions. We further delineate cell type-specific expression of genes associated with chronic kidney disease, diabetes and hypertension, providing insight into possible targeted therapies. This includes expression of a hypertension-associated mechano-sensory ion channel in mesangial cells, and identification of proximal tubule cell populations defined by pathogenic expression signatures. Our fully optimized, quality-controlled transcriptomic profiling pipeline constitutes a tool for the generation of healthy and diseased molecular atlases applicable to clinical samples.
Keyphrases
- single cell
- rna seq
- poor prognosis
- endothelial cells
- chronic kidney disease
- high throughput
- blood pressure
- type diabetes
- cardiovascular disease
- healthcare
- public health
- magnetic resonance imaging
- induced apoptosis
- binding protein
- long non coding rna
- genome wide
- computed tomography
- mental health
- oxidative stress
- stem cells
- cell cycle arrest
- glycemic control
- cell proliferation
- insulin resistance
- endoplasmic reticulum stress
- skeletal muscle
- bone marrow
- bioinformatics analysis
- pi k akt