Age-associated changes in the transcriptomes of non-cultured adipose-derived stem cells from young and old mice assessed via single-cell transcriptome analysis

Yuta Doshida; Haruka Sano; Sadahiro Iwabuchi; Toshiro Aigaki; Masayuki Yoshida; Shinichi Hashimoto; Akihito Ishigami

doi:10.1371/journal.pone.0242171

Age-associated changes in the transcriptomes of non-cultured adipose-derived stem cells from young and old mice assessed via single-cell transcriptome analysis

PLoS One. 2020 Nov 25;15(11):e0242171. doi: 10.1371/journal.pone.0242171. eCollection 2020.

Authors

Yuta Doshida^{1

2}, Haruka Sano^{1

3}, Sadahiro Iwabuchi⁴, Toshiro Aigaki², Masayuki Yoshida³, Shinichi Hashimoto⁴, Akihito Ishigami^{1

2}

Affiliations

¹ Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
² Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, Japan.
³ Department of Life Science and Bioethics, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.

Abstract

Adipose-derived stem cells (ASCs) exhibit self-renewal and pluripotency. The differentiation potency of ASCs has been reported to deteriorate with aging; however, relevant studies used ASCs that were isolated and subcultured several times. It is still unclear whether subcultured ASCs accurately reflect the in vivo state. To address this question, we used freshly isolated stromal vascular fractions (SVFs) and performed comprehensive single-cell transcriptome analysis. In this study, we identified three cell populations as putative ASC candidates in SVFs and three novel ASC-related genes: Adamts7, Snai2, and Tgfbr1, that are reported to be negative regulators of cell differentiation. Moreover, we identified age-associated high gene expression levels of Adamts7, Egfr, and Igfbp4 in the earliest differentiation stage of ASCs. These results suggest that aging may make it impossible to maintain the stringency of the regulation of the expression of some genes related to ASC differentiation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ADAMTS7 Protein / genetics
ADAMTS7 Protein / metabolism
Adipose Tissue / cytology*
Aging / genetics*
Aging / metabolism
Animals
Male
Mesenchymal Stem Cells / metabolism*
Mice
Receptor, Transforming Growth Factor-beta Type I / genetics
Receptor, Transforming Growth Factor-beta Type I / metabolism
Single-Cell Analysis
Snail Family Transcription Factors / genetics
Snail Family Transcription Factors / metabolism
Transcriptome*

Substances

Snai2 protein, mouse
Snail Family Transcription Factors
Receptor, Transforming Growth Factor-beta Type I
Tgfbr1 protein, mouse
ADAMTS7 Protein
Adamts7 protein, mouse

Grants and funding

This study is supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 19H04043 (AI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.