Representation and relative abundance of cell-type selective markers in whole-kidney RNA-Seq data

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

Research output: Contribution to journalArticle

Abstract

Bulk-tissue RNA-Seq is increasingly being used in the study of physiological and pathophysiological processes in the kidney; however, the presence of multiple cell types in kidney tissue complicates data interpretation. We addressed the question of which cell types are represented in whole-kidney RNA-Seq data in order to identify circumstances in which bulk-kidney RNA-Seq can be successfully interpreted. We carried out RNA-Seq in mouse whole kidneys and in microdissected renal tubule segments. To aid in the interpretation of the data, we compiled a database of cell-type selective protein markers for 43 cell types believed to be present in kidney tissue. The whole-kidney RNA-Seq analysis identified transcripts corresponding to 17,742 genes, distributed over 5 orders of magnitude of expression level. Markers for all 43 curated cell types were detectable. Analysis of the cellular makeup of mouse and rat kidney, calculated from published literature, suggests that proximal tubule cells account for more than half of the mRNA in a kidney. Comparison of RNA-Seq data from microdissected proximal tubules with data from whole kidney supports this view. RNA-Seq data for cell-type selective markers in bulk-kidney samples provide a valid means to identify changes in minority-cell abundances in kidney tissue. Because proximal tubules make up a substantial fraction of whole-kidney samples, changes in proximal tubule gene expression can be assessed presumptively by bulk-kidney RNA-Seq, although results could potentially be complicated by the presence of mRNA from other cell types.

Original languageEnglish (US)
Pages (from-to)787-796
Number of pages10
JournalKidney International
Volume95
Issue number4
DOIs
StatePublished - Apr 2019
Externally publishedYes

Fingerprint

RNA
Kidney
Physiological Phenomena
Messenger RNA
Databases
Gene Expression

Keywords

  • bulk tissue
  • proximal tubule
  • transcriptome

ASJC Scopus subject areas

  • Nephrology

Cite this

Representation and relative abundance of cell-type selective markers in whole-kidney RNA-Seq data. / Clark, Jevin Z.; Chen, Lihe; Chou, Chung Lin; Jung, Hyun Jun; Lee, Jae Wook; Knepper, Mark A.

In: Kidney International, Vol. 95, No. 4, 04.2019, p. 787-796.

Research output: Contribution to journalArticle

Clark, Jevin Z. ; Chen, Lihe ; Chou, Chung Lin ; Jung, Hyun Jun ; Lee, Jae Wook ; Knepper, Mark A. / Representation and relative abundance of cell-type selective markers in whole-kidney RNA-Seq data. In: Kidney International. 2019 ; Vol. 95, No. 4. pp. 787-796.
@article{4e51d009cbb34274974f9888c32667f2,
title = "Representation and relative abundance of cell-type selective markers in whole-kidney RNA-Seq data",
abstract = "Bulk-tissue RNA-Seq is increasingly being used in the study of physiological and pathophysiological processes in the kidney; however, the presence of multiple cell types in kidney tissue complicates data interpretation. We addressed the question of which cell types are represented in whole-kidney RNA-Seq data in order to identify circumstances in which bulk-kidney RNA-Seq can be successfully interpreted. We carried out RNA-Seq in mouse whole kidneys and in microdissected renal tubule segments. To aid in the interpretation of the data, we compiled a database of cell-type selective protein markers for 43 cell types believed to be present in kidney tissue. The whole-kidney RNA-Seq analysis identified transcripts corresponding to 17,742 genes, distributed over 5 orders of magnitude of expression level. Markers for all 43 curated cell types were detectable. Analysis of the cellular makeup of mouse and rat kidney, calculated from published literature, suggests that proximal tubule cells account for more than half of the mRNA in a kidney. Comparison of RNA-Seq data from microdissected proximal tubules with data from whole kidney supports this view. RNA-Seq data for cell-type selective markers in bulk-kidney samples provide a valid means to identify changes in minority-cell abundances in kidney tissue. Because proximal tubules make up a substantial fraction of whole-kidney samples, changes in proximal tubule gene expression can be assessed presumptively by bulk-kidney RNA-Seq, although results could potentially be complicated by the presence of mRNA from other cell types.",
keywords = "bulk tissue, proximal tubule, transcriptome",
author = "Clark, {Jevin Z.} and Lihe Chen and Chou, {Chung Lin} and Jung, {Hyun Jun} and Lee, {Jae Wook} and Knepper, {Mark A.}",
year = "2019",
month = "4",
doi = "10.1016/j.kint.2018.11.028",
language = "English (US)",
volume = "95",
pages = "787--796",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Representation and relative abundance of cell-type selective markers in whole-kidney RNA-Seq data

AU - Clark, Jevin Z.

AU - Chen, Lihe

AU - Chou, Chung Lin

AU - Jung, Hyun Jun

AU - Lee, Jae Wook

AU - Knepper, Mark A.

PY - 2019/4

Y1 - 2019/4

N2 - Bulk-tissue RNA-Seq is increasingly being used in the study of physiological and pathophysiological processes in the kidney; however, the presence of multiple cell types in kidney tissue complicates data interpretation. We addressed the question of which cell types are represented in whole-kidney RNA-Seq data in order to identify circumstances in which bulk-kidney RNA-Seq can be successfully interpreted. We carried out RNA-Seq in mouse whole kidneys and in microdissected renal tubule segments. To aid in the interpretation of the data, we compiled a database of cell-type selective protein markers for 43 cell types believed to be present in kidney tissue. The whole-kidney RNA-Seq analysis identified transcripts corresponding to 17,742 genes, distributed over 5 orders of magnitude of expression level. Markers for all 43 curated cell types were detectable. Analysis of the cellular makeup of mouse and rat kidney, calculated from published literature, suggests that proximal tubule cells account for more than half of the mRNA in a kidney. Comparison of RNA-Seq data from microdissected proximal tubules with data from whole kidney supports this view. RNA-Seq data for cell-type selective markers in bulk-kidney samples provide a valid means to identify changes in minority-cell abundances in kidney tissue. Because proximal tubules make up a substantial fraction of whole-kidney samples, changes in proximal tubule gene expression can be assessed presumptively by bulk-kidney RNA-Seq, although results could potentially be complicated by the presence of mRNA from other cell types.

AB - Bulk-tissue RNA-Seq is increasingly being used in the study of physiological and pathophysiological processes in the kidney; however, the presence of multiple cell types in kidney tissue complicates data interpretation. We addressed the question of which cell types are represented in whole-kidney RNA-Seq data in order to identify circumstances in which bulk-kidney RNA-Seq can be successfully interpreted. We carried out RNA-Seq in mouse whole kidneys and in microdissected renal tubule segments. To aid in the interpretation of the data, we compiled a database of cell-type selective protein markers for 43 cell types believed to be present in kidney tissue. The whole-kidney RNA-Seq analysis identified transcripts corresponding to 17,742 genes, distributed over 5 orders of magnitude of expression level. Markers for all 43 curated cell types were detectable. Analysis of the cellular makeup of mouse and rat kidney, calculated from published literature, suggests that proximal tubule cells account for more than half of the mRNA in a kidney. Comparison of RNA-Seq data from microdissected proximal tubules with data from whole kidney supports this view. RNA-Seq data for cell-type selective markers in bulk-kidney samples provide a valid means to identify changes in minority-cell abundances in kidney tissue. Because proximal tubules make up a substantial fraction of whole-kidney samples, changes in proximal tubule gene expression can be assessed presumptively by bulk-kidney RNA-Seq, although results could potentially be complicated by the presence of mRNA from other cell types.

KW - bulk tissue

KW - proximal tubule

KW - transcriptome

UR - http://www.scopus.com/inward/record.url?scp=85062697738&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062697738&partnerID=8YFLogxK

U2 - 10.1016/j.kint.2018.11.028

DO - 10.1016/j.kint.2018.11.028

M3 - Article

C2 - 30826016

AN - SCOPUS:85062697738

VL - 95

SP - 787

EP - 796

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 4

ER -