LncRNAs at the heart of development and disease

Km, Anderson; Anderson, D.M.W.

doi:10.1007/s00335-021-09937-6

“…One of the most highly enriched and abundant lncRNAs in cardiac resident macrophages -lncRNA AI662270, which we termed Schlafenlnc -was shown to be involved in adhesion and migration. As for Schlafenlnc, a particular characteristic of lncRNAs in general is their high degree of cell type-specificity [21][22][23] which makes them important for processes such as development, differentiation of cell types, cellular fate and function (reviewed in 3 ). This characteristic could therefore make lncRNAs the natural choice when describing cell population expression signatures, especially in single cell RNA sequencing (scRNA-seq).…”

Section: Discussionmentioning

confidence: 99%

“…Long non-coding RNAs (lncRNAs) are the largest group of non-coding RNA molecules, with 14,764 lncRNA genes currently annotated in mouse and 19,933 in humans (Gencode in October 2022). Although only a small fraction of these has been functionally characterized, there is strong evidence that lncRNAs, through a variety of mechanisms, adopt critical roles in disease, for example in cancer 1 , metabolic, neurologic 2 and cardiovascular disease 3 . Macrophage lncRNAs in cardiovascular disease have been primarily characterized in the vasculature and within the context of atherosclerosis, e.g., formation of foam cells or polarization (reviewed in 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…Macrophage lncRNAs in cardiovascular disease have been primarily characterized in the vasculature and within the context of atherosclerosis, e.g., formation of foam cells or polarization (reviewed in 4 ). With regard to cardiac disease, the analysis of lncRNAs and their functions has largely focused on cardiomyocytes 5 , endothelial cells 6 and fibroblasts 7 (reviewed in 3 ). By contrast, very little is known about lncRNAs in cardiac resident macrophages (crMPs), although this cell type constitutes the largest population of immune cells in the myocardium during homeostasis and also determines cardiac disease processes (reviewed in 8 ).…”

Section: Introductionmentioning

confidence: 99%

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The lncRNA landscape of cardiac resident macrophages and identification ofSchlafenlncas a regulator of macrophage migratory function

Dueck

¹

,

Althaus

²

,

Heise

³

et al. 2022

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0

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Cardiac resident macrophages (crMPs) were recently shown to exert pivotal functions in cardiac homeostasis and disease, but the underlying molecular mechanisms are largely unclear. Long non-coding RNAs (lncRNAs) are increasingly recognized as important regulatory molecules in a number of cell types, but neither the identity nor the molecular mechanisms of lncRNAs in crMPs are known. Here, we have employed deep RNA-seq and single cell RNA sequencing to resolve the crMP lncRNA landscape from healthy and diseased murine myocardium. CrMPs express previously unknown and highly cell type-specific lncRNAs, among which one lncRNA, termed Schlafenlnc, was particularly abundant and enriched in crMPs. We found Schlafenlnc to be necessary for migration-associated gene expression in macrophages in vitro and in vivo and essential for their adhesion and migration. Collectively, our data provide a basis to the systematic characterization of lncRNAs in crMPs and establish Schlafenlnc as a critical regulator of macrophage migratory functions.

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“…Beyond the developments as reviewed in section 2.3, a further level of complexityi.e. the human epigenome and its life-time dynamics in health and cardiovascular disease [84,[146][147][148][149][150][151][152][153][154][155] -emerged as holding promise for possible therapeutic exploitation [114-120, 156, 157]. At the present time, however, the impact of epigenetic drugs upon clinical medicine is still limited as compared to the nucleic acid drugs discussed above.…”

Section: Continuously Emerging New Levels Of Complexity Of the Human ...mentioning

confidence: 99%

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

Poller¹,

Heidecker²,

Ammirati³

et al. 2022

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0

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During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

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“…Beyond the developments as reviewed in section 2.3, a further level of complexity-i.e. the human epigenome and its life-time dynamics in health and cardiovascular disease [84,[145][146][147][148][149][150][151][152][153][154] -emerged as holding promise for possible therapeutic exploitation [114-120, 155, 156]. At the present time, however, the impact of epigenetic drugs upon clinical medicine is still limited as compared to the nucleic acid drugs discussed above.…”

Section: Continuously Emerging New Levels Of Complexity Of the Human ...mentioning

confidence: 99%

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

Poller¹,

Heidecker²,

Ammirati³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

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LncRNAs at the heart of development and disease

Cited by 17 publications

References 115 publications

The lncRNA landscape of cardiac resident macrophages and identification ofSchlafenlncas a regulator of macrophage migratory function

The lncRNA landscape of cardiac resident macrophages and identification ofSchlafenlncas a regulator of macrophage migratory function

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

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