Abstract
Recently, great progress has been made in single cell genomics and transcriptomics. Here, we present an integrative method, termed single-cell transcriptogenomics (SCTG), in which whole exome sequencing and RNA-seq is performed concurrently on single cells. This methodology enables one to track germline and somatic variants directly from the genome to the transcriptome in individual cells. Mouse embryonic fibroblasts were treated with the powerful mutagen ethylnitrosourea (ENU) and subjected to SCTG. Interestingly, while germline variants were found to be transcribed in an allelically balanced fashion, a significantly different pattern of allelic exclusion was observed for ENU-mutant variants. These results suggest that the adverse effects of induced mutations, in contrast to germline variants, may be mitigated by allelically biased transcription. They also illustrate how SCTG can be instrumental in the direct assessment of phenotypic consequences of genomic variants.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 55-62 |
| Number of pages | 8 |
| Journal | Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis |
| Volume | 772 |
| DOIs | |
| State | Published - Feb 1 2015 |
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Keywords
- Allelic exclusion
- ENU
- Germline mutations
- Next generation sequencing
- Single cell transcriptogenomics
- Somatic mutations
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Health, Toxicology and Mutagenesis
Cite this
Single-cell transcriptogenomics reveals transcriptional exclusion of ENU-mutated alleles. / Li, Wenge; Calder, R. Brent; Mar, Jessica C.; Vijg, Jan.
In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 772, 01.02.2015, p. 55-62.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Single-cell transcriptogenomics reveals transcriptional exclusion of ENU-mutated alleles
AU - Li, Wenge
AU - Calder, R. Brent
AU - Mar, Jessica C.
AU - Vijg, Jan
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Recently, great progress has been made in single cell genomics and transcriptomics. Here, we present an integrative method, termed single-cell transcriptogenomics (SCTG), in which whole exome sequencing and RNA-seq is performed concurrently on single cells. This methodology enables one to track germline and somatic variants directly from the genome to the transcriptome in individual cells. Mouse embryonic fibroblasts were treated with the powerful mutagen ethylnitrosourea (ENU) and subjected to SCTG. Interestingly, while germline variants were found to be transcribed in an allelically balanced fashion, a significantly different pattern of allelic exclusion was observed for ENU-mutant variants. These results suggest that the adverse effects of induced mutations, in contrast to germline variants, may be mitigated by allelically biased transcription. They also illustrate how SCTG can be instrumental in the direct assessment of phenotypic consequences of genomic variants.
AB - Recently, great progress has been made in single cell genomics and transcriptomics. Here, we present an integrative method, termed single-cell transcriptogenomics (SCTG), in which whole exome sequencing and RNA-seq is performed concurrently on single cells. This methodology enables one to track germline and somatic variants directly from the genome to the transcriptome in individual cells. Mouse embryonic fibroblasts were treated with the powerful mutagen ethylnitrosourea (ENU) and subjected to SCTG. Interestingly, while germline variants were found to be transcribed in an allelically balanced fashion, a significantly different pattern of allelic exclusion was observed for ENU-mutant variants. These results suggest that the adverse effects of induced mutations, in contrast to germline variants, may be mitigated by allelically biased transcription. They also illustrate how SCTG can be instrumental in the direct assessment of phenotypic consequences of genomic variants.
KW - Allelic exclusion
KW - ENU
KW - Germline mutations
KW - Next generation sequencing
KW - Single cell transcriptogenomics
KW - Somatic mutations
UR - http://www.scopus.com/inward/record.url?scp=84922635277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922635277&partnerID=8YFLogxK
U2 - 10.1016/j.mrfmmm.2015.01.002
DO - 10.1016/j.mrfmmm.2015.01.002
M3 - Article
C2 - 25733965
AN - SCOPUS:84922635277
VL - 772
SP - 55
EP - 62
JO - Mutation Research
JF - Mutation Research
SN - 0027-5107
ER -