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通过单细胞转录组分析评估来自年轻和老年小鼠的未培养脂肪源性干细胞的转录组随年龄的变化。

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

机构信息

Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, Japan.

出版信息

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

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.

摘要

脂肪干细胞 (ASCs) 具有自我更新和多能性。已有报道称,ASCs 的分化潜能随年龄增长而下降;然而,相关研究使用的是经过多次分离和传代的 ASCs。目前尚不清楚经过传代的 ASCs 是否能准确反映体内状态。为了解决这个问题,我们使用了新鲜分离的基质血管部分 (SVFs) 并进行了全面的单细胞转录组分析。在这项研究中,我们在 SVFs 中鉴定出了三个细胞群体作为潜在的 ASC 候选细胞,并发现了三个新的与 ASC 相关的基因:Adamts7、Snai2 和 Tgfbr1,它们被报道是细胞分化的负调控因子。此外,我们还发现 Adamts7、Egfr 和 Igfbp4 的基因表达水平在 ASCs 的最早分化阶段随年龄的增长而升高。这些结果表明,衰老可能使一些与 ASC 分化相关的基因表达调控的严格性变得不可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612a/7688117/c5a0ec59a850/pone.0242171.g001.jpg

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