Single-cell and single-nucleus RNA-sequencing from paired normal-adenocarcinoma lung samples provide both common and discordant biological insights Article Swipe
Sébastien Renaut
,
Victoria Saavedra Armero
,
Dominique K. Boudreau
,
Nathalie Gaudreault
,
Patrice Desmeules
,
Sébastien Thériault
,
Patrick Mathieu
,
Philippe Joubert
,
Yohan Bossé
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pgen.1011301
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pgen.1011301
Whether single-cell RNA-sequencing (scRNA-seq) captures the same biological information as single-nucleus RNA-sequencing (snRNA-seq) remains uncertain and likely to be context-dependent. Herein, a head-to-head comparison was performed in matched normal-adenocarcinoma human lung samples to assess biological insights derived from scRNA-seq versus snRNA-seq and better understand the cellular transition that occurs from normal to tumoral tissue. Here, the transcriptome of 160,621 cells/nuclei was obtained. In non-tumor lung, cell type proportions varied widely between scRNA-seq and snRNA-seq with a predominance of immune cells in the former (81.5%) and epithelial cells (69.9%) in the later. Similar results were observed in adenocarcinomas, in addition to an overall increase in cell type heterogeneity and a greater prevalence of copy number variants in cells of epithelial origin, which suggests malignant assignment. The cell type transition that occurs from normal lung tissue to adenocarcinoma was not always concordant whether cells or nuclei were examined. As expected, large differential expression of the whole-cell and nuclear transcriptome was observed, but cell-type specific changes of paired normal and tumor lung samples revealed a set of common genes in the cells and nuclei involved in cancer-related pathways. In addition, we showed that the ligand-receptor interactome landscape of lung adenocarcinoma was largely different whether cells or nuclei were evaluated. Immune cell depletion in fresh specimens partly mitigated the difference in cell type composition observed between cells and nuclei. However, the extra manipulations affected cell viability and amplified the transcriptional signatures associated with stress responses. In conclusion, research applications focussing on mapping the immune landscape of lung adenocarcinoma benefit from scRNA-seq in fresh samples, whereas snRNA-seq of frozen samples provide a low-cost alternative to profile more epithelial and cancer cells, and yield cell type proportions that more closely match tissue content.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pgen.1011301
- https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1011301&type=printable
- OA Status
- gold
- Cited By
- 8
- References
- 47
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4399169176
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4399169176Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1371/journal.pgen.1011301Digital Object Identifier
- Title
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Single-cell and single-nucleus RNA-sequencing from paired normal-adenocarcinoma lung samples provide both common and discordant biological insightsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-05-30Full publication date if available
- Authors
-
Sébastien Renaut, Victoria Saavedra Armero, Dominique K. Boudreau, Nathalie Gaudreault, Patrice Desmeules, Sébastien Thériault, Patrick Mathieu, Philippe Joubert, Yohan BosséList of authors in order
- Landing page
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https://doi.org/10.1371/journal.pgen.1011301Publisher landing page
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https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1011301&type=printableDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1011301&type=printableDirect OA link when available
- Concepts
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Biology, Transcriptome, Adenocarcinoma, Cell, RNA, Cell type, Cell nucleus, Gene, Molecular biology, Genetics, Cell biology, Cancer, Gene expressionTop concepts (fields/topics) attached by OpenAlex
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-
8Total citation count in OpenAlex
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2025: 6, 2024: 2Per-year citation counts (last 5 years)
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47Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W2771542157, https://openalex.org/W2865352686, https://openalex.org/W3198511950, https://openalex.org/W4379879135, https://openalex.org/W3004765765, https://openalex.org/W3161550248, https://openalex.org/W2936414047, https://openalex.org/W2759615793, https://openalex.org/W2980870655, https://openalex.org/W2279350325, https://openalex.org/W3015184839, https://openalex.org/W3023126733, https://openalex.org/W2902647266, https://openalex.org/W3030739213, https://openalex.org/W2906213364, https://openalex.org/W2734414396, https://openalex.org/W3213918788, https://openalex.org/W3212143351, https://openalex.org/W2808837841, https://openalex.org/W3078555423, https://openalex.org/W4200168331, https://openalex.org/W3022968840, https://openalex.org/W3044347277, https://openalex.org/W3197945601, https://openalex.org/W4392231446, https://openalex.org/W3164692211, https://openalex.org/W2138094019, https://openalex.org/W4367296429, https://openalex.org/W3208953781, https://openalex.org/W2949237386, https://openalex.org/W2922020904, https://openalex.org/W1989734503, https://openalex.org/W2150985086, https://openalex.org/W1982488143, https://openalex.org/W4298008223, https://openalex.org/W4378802283, https://openalex.org/W2951158909, https://openalex.org/W2953151710, https://openalex.org/W2949177718, https://openalex.org/W1987971958, https://openalex.org/W3202649987, https://openalex.org/W2179438025, https://openalex.org/W4391447275, https://openalex.org/W2572174216, https://openalex.org/W2582743722, https://openalex.org/W3099559583, https://openalex.org/W2560367415 |
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| corresponding_author_ids | https://openalex.org/A5081112788, https://openalex.org/A5027278761, https://openalex.org/A5091615631, https://openalex.org/A5066920785, https://openalex.org/A5077109568, https://openalex.org/A5057285899, https://openalex.org/A5045378276, https://openalex.org/A5071026604, https://openalex.org/A5011296618 |
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