A Landscape of Murine Long Non-Coding RNAs Reveals the Leading Transcriptome Alterations in Adipose Tissue during Aging

Zhou, Qi; Wan, Qianfen; Jiang, Yuxi; Liu, Jin; Li, Qiang; Sun, Li

doi:10.1016/j.celrep.2020.107694

Cited by 29 publications

(20 citation statements)

References 58 publications

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“…This affects all tissues and can modify disease processes. For instance, during aging, certain lncRNAs are generated in white AT which are linked to inflammatory pathways implicating AT and obesity with age-related degenerative changes ( 72 ). In another example, pyroptosis, a process involving activation of the inflammasome, is controlled by the lncRNA NEAT1 in diabetic nephropathy through the action of the mir34c/NLRP3 axis ( 73 ).…”

Section: Insulin Resistance Inflammation and Diabetesmentioning

confidence: 99%

The Role of Inflammation in Diabetic Retinopathy

2020

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Inflammation is central to pathogenic processes in diabetes mellitus and the metabolic syndrome and particularly implicates innate immunity in the development of complications. Inflammation is a primary event in Type 1 diabetes where infectious (viral) and/or autoimmune processes initiate disease; in contrast, chronic inflammation is typical in Type 2 diabetes and is considered a sequel to increasing insulin resistance and disturbed glucose metabolism. Diabetic retinopathy (DR) is perceived as a vascular and neurodegenerative disease which occurs after some years of poorly controlled diabetes. However, many of the clinical features of DR are late events and reflect the nature of the retinal architecture and its cellular composition. Retinal microvascular disease is, in fact, an early event pathogenetically, induced by low grade, persistent leukocyte activation which causes repeated episodes of capillary occlusion and, progressive, attritional retinal ischemia. The later, overt clinical signs of DR are a consequence of the retinal ischemia. Metabolic dysregulation involving both lipid and glucose metabolism may lead to leukocyte activation. On a molecular level, we have shown that macrophage-restricted protein tyrosine phosphatase 1B (PTP1B) is a key regulator of inflammation in the metabolic syndrome involving insulin resistance and it is possible that PTP1B dysregulation may underlie retinal microvascular disease. We have also shown that adherent CCR5 + CD11b + monocyte macrophages appear to be selectively involved in retinal microvascular occlusion. In this review, we discuss the relationship between early leukocyte activation and the later features of DR, common pathogenetic processes between diabetic microvascular disease and other vascular retinopathies, the mechanisms whereby leukocyte activation is induced in hyperglycemia and dyslipidemia, the signaling mechanisms involved in diabetic microvascular disease, and possible interventions which may prevent these retinopathies. We also address a possible role for adaptive immunity in DR. Although significant improvements in treatment of DR have been made with intravitreal anti-VEGF therapy, a sizeable proportion of patients, particularly with sight-threatening macular edema, fail to respond. Alternative therapies targeting inflammatory processes may offer an advantage.

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Section: Insulin Resistance Inflammation and Diabetesmentioning

confidence: 99%

The Role of Inflammation in Diabetic Retinopathy

2020

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“…Two main factors likely lead to the in vivo heterogeneity of senescent cells. First, during the RNA-sequencing analysis of gene expression changes in various mouse organs, most aging-related changes were grouped by organ (Zhou et al, 2020). However, the different organs have varying epigenetic programs and microenvironments and undergo diverging aging processes (Ashapkin et al, 2017).…”

Section: In Vivo Transcriptomic Study Of Senescent Cellmentioning

confidence: 99%

Transcriptomic Analysis of Cellular Senescence: One Step Closer to Senescence Atlas

Kim

2021

Molecules and Cells

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Senescent cells that gradually accumulate during aging are one of the leading causes of aging. While senolytics can improve aging in humans as well as mice by specifically eliminating senescent cells, the effect of the senolytics varies in different cell types, suggesting variations in senescence. Various factors can induce cellular senescence, and the rate of accumulation of senescent cells differ depending on the organ. In addition, since the heterogeneity is due to the spatiotemporal context of senescent cells, in vivo studies are needed to increase the understanding of senescent cells. Since current methods are often unable to distinguish senescent cells from other cells, efforts are being made to find markers commonly expressed in senescent cells using bulk RNA-sequencing. Moreover, single-cell RNA (scRNA) sequencing, which analyzes the transcripts of each cell, has been utilized to understand the in vivo characteristics of the rare senescent cells. Recently, transcriptomic cell atlases for each organ using this technology have been published in various species. Novel senescent cells that do not express previously established marker genes have been discovered in some organs. However, there is still insufficient information on senescent cells due to the limited throughput of the scRNA sequencing technology. Therefore, it is necessary to improve the throughput of the scRNA sequencing technology or develop a way to enrich the rare senescent cells. The in vivo senescent cell atlas that is established using rapidly developing single-cell technologies will contribute to the precise rejuvenation by specifically removing senescent cells in each tissue and individual.

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“…snRNA-seq intrinsically enriches for nuclear localized transcripts, and previous studies have reported enrichment of lncRNAs in snRNA-seq libraries over scRNA-seq (Grindberg et al 2013;Zeng et al 2016). We hypothesized that nuclear enrichment of lncRNAs could be advantageous for characterizing adipose tissue because multiple lncRNAs have also been implicated in regulating adipogenesis (Sun et al 2013;Ding et al 2018;Wei et al 2016;Sun and Lin 2019;Zhou et al 2020). We tested this hypothesis in our in vitro system by profiling adipogenic regulatory lncRNAs in our whole-cell and nuclear libraries derived from white preadipocytes, after normalization.…”

Section: Gene Length-associated Detection Bias In Single-nuclei Rna-smentioning

confidence: 97%

Characterization of transcript enrichment and detection bias in single-nuclei RNA-seq for mapping of distinct human adipocyte lineages

Gupta

Shamsi

Altemos

et al. 2021

Preprint

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Single-cell RNA-sequencing (scRNA-seq) enables molecular characterization of complex biological tissues at high resolution. The requirement of single-cell extraction, however, makes it challenging for profiling tissues such as adipose tissue where collection of intact single adipocytes is complicated by their fragile nature. For such tissues, single-nuclei extraction is often much more efficient and therefore single-nuclei RNA-sequencing (snRNA-seq) presents an alternative to scRNA-seq. However, nuclear transcripts represent only a fraction of the transcriptome in a single cell, with snRNA-seq marked with inherent transcript enrichment and detection biases. Therefore, snRNA-seq may be inadequate for mapping important transcriptional signatures in adipose tissue. In this study, we compare the transcriptomic landscape of single nuclei isolated from preadipocytes and mature adipocytes across human white and brown adipocyte lineages, with whole-cell transcriptome. We demonstrate that snRNA-seq is capable of identifying the broad cell types present in scRNA-seq at all states of adipogenesis. However, we also explore how and why the nuclear transcriptome is biased and limited, and how it can be advantageous. We robustly characterize the enrichment of nuclear-localized transcripts and adipogenic regulatory lncRNAs in snRNA-seq, while also providing a detailed understanding for the preferential detection of long genes upon using this technique. To remove such technical detection biases, we propose a normalization strategy for a more accurate comparison of nuclear and cellular data. Finally, we demonstrate successful integration of scRNA-seq and snRNA-seq datasets with existing bioinformatic tools. Overall, our results illustrate the applicability of snRNA-seq for characterization of cellular diversity in the adipose tissue.

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A Landscape of Murine Long Non-Coding RNAs Reveals the Leading Transcriptome Alterations in Adipose Tissue during Aging

Cited by 29 publications

References 58 publications

The Role of Inflammation in Diabetic Retinopathy

The Role of Inflammation in Diabetic Retinopathy

Transcriptomic Analysis of Cellular Senescence: One Step Closer to Senescence Atlas

Characterization of transcript enrichment and detection bias in single-nuclei RNA-seq for mapping of distinct human adipocyte lineages

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