Dueck, H and Khaladkar, M and Kim, TK and Spaethling, JM and Francis, C and Suresh, S and Fisher, SA and Seale, P and Beck, SG and Bartfai, T and Kuhn, B and Eberwine, J and Kim, J
(2015)
Deep sequencing reveals cell-type-specific patterns of single-cell transcriptome variation.
Genome Biology, 16 (1).
ISSN 1474-7596
Abstract
Background: Differentiation of metazoan cells requires execution of different gene expression programs but recent single-cell transcriptome profiling has revealed considerable variation within cells of seeming identical phenotype. This brings into question the relationship between transcriptome states and cell phenotypes. Additionally, single-cell transcriptomics presents unique analysis challenges that need to be addressed to answer this question. Results: We present high quality deep read-depth single-cell RNA sequencing for 91 cells from five mouse tissues and 18 cells from two rat tissues, along with 30 control samples of bulk RNA diluted to single-cell levels. We find that transcriptomes differ globally across tissues with regard to the number of genes expressed, the average expression patterns, and within-cell-type variation patterns. We develop methods to filter genes for reliable quantification and to calibrate biological variation. All cell types include genes with high variability in expression, in a tissue-specific manner. We also find evidence that single-cell variability of neuronal genes in mice is correlated with that in rats consistent with the hypothesis that levels of variation may be conserved. Conclusions: Single-cell RNA-sequencing data provide a unique view of transcriptome function; however, careful analysis is required in order to use single-cell RNA-sequencing measurements for this purpose. Technical variation must be considered in single-cell RNA-sequencing studies of expression variation. For a subset of genes, biological variability within each cell type appears to be regulated in order to perform dynamic functions, rather than solely molecular noise.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Dueck, H | | | | Khaladkar, M | | | | Kim, TK | | | | Spaethling, JM | | | | Francis, C | | | | Suresh, S | | | | Fisher, SA | | | | Seale, P | | | | Beck, SG | | | | Bartfai, T | | | | Kuhn, B | | | | Eberwine, J | | | | Kim, J | | | |
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Date: |
9 June 2015 |
Date Type: |
Publication |
Journal or Publication Title: |
Genome Biology |
Volume: |
16 |
Number: |
1 |
DOI or Unique Handle: |
10.1186/s13059-015-0683-4 |
Schools and Programs: |
School of Medicine > Pediatrics |
Refereed: |
Yes |
ISSN: |
1474-7596 |
Date Deposited: |
17 Aug 2016 13:23 |
Last Modified: |
30 Mar 2021 13:56 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/29258 |
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