Cell-Type Selective Markers Represented in Whole-Kidney RNA-Seq Data

Clark, Jevin Z.; Chen, Lihe; Chou, Chung‐Lin; Jung, Hyun Jun; Lee, Jae Woo; Knepper, Mark A.

doi:10.1101/348615

Cited by 5 publications

(4 citation statements)

References 34 publications

(60 reference statements)

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“…Although cell type-specific markers for 43 kidney cell types can be detected in whole-kidney RNA-Seq data, transcriptional changes observed with whole-kidney RNA-Seq cannot be attributed to a particular cell type (11). Proximal tubule cells represent the dominant cell type in the kidney and contribute the majority of whole-kidney mRNA (11). By comparison, CNT/CD cells represent a small percentage of the total kidney cell population (31).…”

Section: Determination Of Kidney Tubule Segment-specific Expression Of L1-cammentioning

confidence: 99%

Salt-sensitive transcriptome of isolated kidney distal tubule cells

Swanson

Nelson

Jeng

et al. 2019

Physiological Genomics

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In the distal kidney tubule, the steroid hormone aldosterone regulates sodium reabsorption via the epithelial sodium channel (ENaC). Most studies seeking to identify ENaC-regulating aldosterone-induced proteins have used transcriptional profiling of cultured cells. To identify salt-sensitive transcripts in an in vivo model, we used low-NaCl or high-NaCl diet to stimulate or suppress endogenous aldosterone, in combination with magnetic- and fluorescence-activated cell sorting to isolate distal tubule cells from mouse kidney for transcriptional profiling. Of the differentially expressed transcripts, 162 were more abundant in distal tubule cells isolated from mice fed low-NaCl diet, and 161 were more abundant in distal tubule cells isolated from mice fed high-NaCl diet. Enrichment analysis of Gene Ontology biological process terms identified multiple statistically overrepresented pathways among the differentially expressed transcripts that were more abundant in distal tubule cells isolated from mice fed low-NaCl diet, including ion transmembrane transport, regulation of growth, and negative regulation of apoptosis. Analysis of Gene Ontology molecular function terms identified differentially expressed transcription factors, transmembrane transporters, kinases, and G protein-coupled receptors. Finally, comparison with a recently published study of gene expression changes in distal tubule cells in response to administration of aldosterone identified 18 differentially expressed genes in common between the two experiments. When expression of these genes was measured in cortical collecting ducts microdissected from mice fed low-NaCl or high-NaCl diet, eight were differentially expressed. These genes are likely to be regulated directly by aldosterone and may provide insight into aldosterone signaling to ENaC in the distal tubule.

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Section: Determination Of Kidney Tubule Segment-specific Expression Of L1-cammentioning

confidence: 99%

Salt-sensitive transcriptome of isolated kidney distal tubule cells

Swanson

Nelson

Jeng

et al. 2019

Physiological Genomics

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“…Cell-type selective markers in Supplemental Figures 9-11 were based on ref. 38. RNA-Seq data and part of Ribo-Seq data were analyzed using edgeR (Figure 7A, Figure 9, A-I, and Supplemental Figure 15B).…”

Section: Acknowledgmentsmentioning

confidence: 99%

Bacterial sepsis triggers an antiviral response that causes translation shutdown

Hato¹,

Maier²,

Syed³

et al. 2018

Journal of Clinical Investigation

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“…The kidney contains at least 43 cell types (1), each with its own characteristic transcriptome and proteome. Discovery of pathophysiological mechanisms, therefore, requires isolation or enrichment of the cell types responsible for specific disease processes.…”

Section: Introductionmentioning

confidence: 99%

RNA-Seq and Protein Mass Spectrometry in Microdissected Kidney Tubules Reveal Signaling Processes that Initiate Lithium-Induced Diabetes Insipidus

Sung

Chen

Limbutara

et al. 2018

Preprint

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1Lithium salts, used for treatment of bipolar disorder, frequently induce nephrogenic diabetes insipidus (NDI), limiting therapeutic success. NDI is associated with loss of expression of the molecular water channel, aquaporin-2, in the renal collecting duct (CD). Here, we use the methods of systems biology in a well-established rat model of lithium-induced NDI to identify signaling pathways activated at the onset of polyuria. Using single-tubule RNA-Seq, full transcriptomes were determined in microdissected cortical CDs of rats 72 hrs after initiation of lithium chloride (LiCl) administration (vs. timecontrols without LiCl). Transcriptome-wide changes in mRNA abundances were mapped to gene sets associated with curated canonical signaling pathways, showing evidence for activation of NF-κB signaling with induction of genes coding for multiple chemokines as well as most components of the Major Histocompatibility Complex (MHC) Class I antigen-presenting complex. Administration of antiinflammatory doses of dexamethasone to LiCl-treated rats countered the loss of aquaporin-2 protein.RNA-Seq also confirmed prior evidence of a shift from quiescence into the cell cycle with arrest. Time course studies demonstrated an early (12 hrs) increase in multiple immediate early genes including several transcription factors. Protein mass spectrometry in microdissected cortical CDs provided corroborative evidence but also identified decreased abundance of several anti-oxidant proteins.Integration of new data with prior data about lithium effects at a molecular level leads to a signaling model in which lithium increases ERK activation leading to induction of NF-κB signaling and an inflammatory-like response that represses Aqp2 gene transcription. 1 Note on terminology: Except where indicated we use official gene symbols to refer to proteins (All caps), transcripts, and genes (italicized), e.g. AQP2 (protein), Aqp2 (transcript), Aqp2 (gene). RESULTSGeneral characteristics of animal model. Using a standard model of lithium-induced NDI in rats (8), we carried out preliminary studies with immunoblotting to identify when, after starting lithium chloride (LiCl), there was a consistently detectable decrease in renal AQP2 protein abundance. Making initial observations at 0, 24, 48, 72, and 96 hrs of LiCl administration (Figure 1A and 1B) followed by multiple-replicate immunoblotting at 72 hrs and 96 hrs (Figure 1C and D), we conclude that there is a demonstrable decrease in AQP2 protein abundance at least by 72 hrs. LiCl-treated rats showed significantly increased water intake within the first 24 hrs (Figure 2A), and urine osmolality was significantly decreased in LiCl-treated rats by the 48-hr juncture ( Figure 2B). After 72 hrs (Table 1), there was no significant difference in body weight between the LiCl and control groups. There was a small increase in serum urea, consistent with pre-renal azotemia in LiCl-treated rats. However, serum creatinine, sodium, chloride, and total carbon dioxide values were unchanged. Also, there was no change i...

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Cell-Type Selective Markers Represented in Whole-Kidney RNA-Seq Data

Cited by 5 publications

References 34 publications

Salt-sensitive transcriptome of isolated kidney distal tubule cells

Salt-sensitive transcriptome of isolated kidney distal tubule cells

Bacterial sepsis triggers an antiviral response that causes translation shutdown

RNA-Seq and Protein Mass Spectrometry in Microdissected Kidney Tubules Reveal Signaling Processes that Initiate Lithium-Induced Diabetes Insipidus

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