Single senescent cell sequencing reveals heterogeneity in senescent cells induced by telomere erosion

Tang, Herman; Geng, Anke; Zhang, Tengjiao; Wang, Chen; Jiang, Ying; Mao, Zhiyong

doi:10.1007/s13238-018-0591-y

Cited by 36 publications

(45 citation statements)

References 13 publications

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“…Furthermore, RS VSMCs retain MYH11 and TAGLN expression, which is also consistent with previous studies for TAGLN (Miao et al, 2017). These results are in line with recent research showing heterogeneity of senescent cells (van Deursen, 2014;Olivieri et al, 2018;Tang et al, 2019), and warrant future study on a single-cell level (Olivieri et al, 2018).…”

Section: Discussionsupporting

confidence: 91%

Inflammatory Drivers of Cardiovascular Disease: Molecular Characterization of Senescent Coronary Vascular Smooth Muscle Cells

et al. 2020

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Stojanović et al. Vascular Smooth Muscle Cell Senescence deregulation to warrant senescent VSMC detection, we have conducted a non-biased proteomics and in silico analysis of RS VSMC demonstrating altered RNA biology as the central molecular feature of senescence in this cell type. Therefore, key proteins involved with RNA functionality, HMGB-1 release, LMNB-1 downregulation, in junction with nuclear enlargement, can be used as markers of VSMC senescence, enabling the detection of these pathogenic pro-inflammatory cells in future therapeutic studies in ischemic heart disease and atherosclerosis.

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Section: Discussionsupporting

confidence: 91%

Inflammatory Drivers of Cardiovascular Disease: Molecular Characterization of Senescent Coronary Vascular Smooth Muscle Cells

et al. 2020

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“…setup: FACS-sorting for muscle stem marker; bead transcription & amplification using Smartseq2 Remarks: Quiescent cells were investigated, and accordingly, no change in expression of senescence markers Cdkn2a (p16) & Cdkn1b (p27) was observed. In-vitro datasets HCA2 Fibroblast Atlas ( Tang et al, 2019 ) Tissues: HCA2 fibroblasts, after replicative senescence after 38, 48 and 71 population doublings Animals/Cells: 1 200 + 400 human cells Heterogeneity: Not investigated Exp. setup: Drop-seq; Library prep: Illumina Nextera XT Remarks: Investigation of senescence (beta-galactosidase, rate of EdU incorporation), role of telomeres.…”

Section: Single-cell Analyses Of Aging and Senescencementioning

confidence: 99%

“…Telomere erosion was investigated by the in-vitro study of senescent cells reported in ( Tang et al, 2019 ). They cultured HCA2 fibroblasts until replicative senescence was reached and performed single cell transcriptomics on a total of 1200 cells from early, middle and late passage.…”

Section: Single-cell Analyses Of Aging and Senescencementioning

confidence: 99%

“…This is a further confirmation that, to a certain degree, cellular senescence is not only different in different cell types, but also depends on the stressor that caused the senescent state. Nevertheless, ( Tang et al, 2019 ) identify a senescence core signature of up-regulated genes that include p21 (CDKN1A) and members of the SASP.…”

Section: Single-cell Analyses Of Aging and Senescencementioning

confidence: 99%

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Single-cell analyses of aging, inflammation and senescence

Uyar

Palmer

Kowald

et al. 2020

Ageing Research Reviews

115

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Highlights A comprehensive tabulation of aging-related single-cell studies published to date. Often, the fraction of cells expressing senescence markers increases with age. Inflammaging is observed in many datasets, driven by specific cells such as Kupffer cells in the liver. Single-cell transcriptomics will enable new experiments and insights by intervention studies.

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“…This suggests that non-growing cells in both control and NAC groups may be quiescent, senescent or a combination of both. Indeed, PCA plots based on senescence and quiescent marker genes identified from a previously published study 26 showed separation between growing and non-growing cells ( Figure 6E Table S6). These analyses suggest that these non-growing cells contain a mix of quiescent and senescent cells and those did not grow after 13 days of NAC treatment are likely enriched for senescent cells.…”

Section: Transcriptional Analysis Of Growing and Non-growing Single Cmentioning

confidence: 74%

A small molecule screen identified N-Acetyl-L-cysteine for promotingex vivogrowth of single circulating tumor cells

Teng

Kamal

Iriondo

et al. 2020

Preprint

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Circulating tumor cells (CTCs) can be isolated via a minimally invasive blood draw and are considered a liquid biopsy of their originating solid tumors. CTCs contain a small subset of metastatic precursors that can form metastases in secondary organs, and provide a resource to identify mechanisms underlying metastasis-initiating properties. Despite technological advancements that allow for highly sensitive approaches of detection and isolation, CTCs are very rare and often present as single cells, posing an extreme challenge for ex vivo expansion after isolation. Here, using previously established patient-derived CTC lines, we performed a small molecule drug screening to identify compounds that can improve ex vivo culture efficiency for single CTCs. We found that N-acetylcysteine (NAC) and other antioxidants can promote ex vivo expansion of single CTCs, by reducing oxidative and other stress particularly at the initial stage of single cell expansion. RNA-seq analysis of growing clones and non-growing clones confirmed the effect by NAC, but also indicate that NAC-induced decrease in oxidative stress is insufficient for promoting proliferation of a subset of cells with heterogeneous quiescent and senescent features. Despite the challenge in expanding all CTCs, NAC treatment lead to establishment of single CTC clones that have similar tumorigenic features, which will facilitate future functional analyses.

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Single senescent cell sequencing reveals heterogeneity in senescent cells induced by telomere erosion

Cited by 36 publications

References 13 publications

Inflammatory Drivers of Cardiovascular Disease: Molecular Characterization of Senescent Coronary Vascular Smooth Muscle Cells

Inflammatory Drivers of Cardiovascular Disease: Molecular Characterization of Senescent Coronary Vascular Smooth Muscle Cells

Single-cell analyses of aging, inflammation and senescence

A small molecule screen identified N-Acetyl-L-cysteine for promotingex vivogrowth of single circulating tumor cells

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