Lack of evidence for increased transcriptional noise in aged tissues
- Biodonostia Health Research Institute, Spain
Abstract
Aging is often associated with a loss of cell type identity that results in an increase in transcriptional noise in aged tissues. If this phenomenon reflects a fundamental property of aging remains an open question. Transcriptional changes at the cellular level are best detected by single-cell RNA sequencing (scRNAseq). However, the diverse computational methods used for the quantification of age-related loss of cellular identity have prevented reaching meaningful conclusions by direct comparison of existing scRNAseq datasets. To address these issues we created Decibel, a Python toolkit that implements side-to-side four commonly used methods for the quantification of age-related transcriptional noise in scRNAseq data. Additionally, we developed Scallop, a novel computational method for the quantification of membership of single cells to their assigned cell type cluster. Cells with a greater Scallop membership score are transcriptionally more stable. Application of these computational tools to seven aging datasets showed large variability between tissues and datasets, suggesting that increased transcriptional noise is not a universal hallmark of aging. To understand the source of apparent loss of cell type identity associated with aging, we analyzed cell type-specific changes in transcriptional noise and the changes in cell type composition of the mammalian lung. No robust pattern of cell type-specific transcriptional noise alteration was found across aging lung datasets. In contrast, age-associated changes in cell type composition of the lung were consistently found, particularly of immune cells. These results suggest that claims of increased transcriptional noise of aged tissues should be reformulated.
Data availability
Code availabilityThe Decibel and Scallop repositories can be found at https://gitlab.com/olgaibanez/decibel and https: //gitlab.com/olgaibanez/scallop, respectively. The reproducible Jupyter notebooks with the analyses carried out in this study can be found in figshare (https://doi.org/10.6084/m9.figshare.20402817.v1).
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scRNAseq dataset of murine aging lungGene Expression Omnibus, GSE124872.
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scRNAseq dataset of murine aging lung, spleen and kidneyGene Expression Omnibus, GSE132901.
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Human Lung Cell AtlasSynapse, syn21041850.
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scRNAseq datasets of adult mammalian lungsGene Expression Omnibus, GSE133747.
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scRNAseq dataset of human aging pancreasGene Expression Omnibus, GSE81547.
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scRNAseq dataset of human aging skinGene Expression Omnibus, GSE130973.
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scRNAseq dataset of murine aging brainGene Expression Omnibus, GSE129788.
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scRNAseq dataset of murine aging dermal fibroblastsGene Expression Omnibus, GSE111136.
Article and author information
Author details
Funding
la Caixa" Foundation " (LCF/BQ/IN18/11660065)
- Olga Ibañez-Solé
Instituto de Salud Carlos III (AC17/00012)
- Olga Ibañez-Solé
- Alex M Ascensión
- Ander Izeta
Instituto de Salud Carlos III (PI19/01621)
- Olga Ibañez-Solé
- Alex M Ascensión
- Ander Izeta
Ministerio de Ciencia e Innovación (PID2020-119715GB-I00)
- Olga Ibañez-Solé
- Alex M Ascensión
- Ander Izeta
European Regional Development Fund (MCIN/AEI/10.13039/501100011033)
- Olga Ibañez-Solé
- Alex M Ascensión
- Ander Izeta
H2020 Marie Skłodowska-Curie Actions (713673)
- Olga Ibañez-Solé
Eusko Jaurlaritza (PRE_2020_2_0081)
- Alex M Ascensión
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Ibañez-Solé et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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