The 2021 version of the gene table of neuromuscular disorders (nuclear genome)

Benarroch, Louise; Bonne, Gisèle; Rivier, François; Hamroun, Dalil

doi:10.1016/j.nmd.2020.11.009

Cited by 53 publications

(55 citation statements)

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“…We demonstrated the utility of a tissue atlas for monogenic disease biology, where we inferred the primary and secondary pathobiology of monogenic muscle diseases by analyzing skeletal, cardiac and smooth muscle. Disease groups were enriched not only for genes expressed in myocytes, but also for non-myocytes, including nervous system, immune and stromal cells (Benarroch et al, 2020). Note that we observed multiple subtypes of myocytes within one tissue, including cytoplasmic myocytes (high myoglobin (MB) expression and exon:intron ratio), which suggests possible specialization of different nuclei in one syncytium.…”

Section: Discussionmentioning

confidence: 73%

“…While human genetics has successfully identified many rare monogenic disease genes, the cell type(s) of action are often unknown, or can even be incorrect, as shown for CFTR, the gene underlying cystic fibrosis (Montoro et al, 2018;Plasschaert et al, 2018). Leveraging the three muscle types in our atlas-cardiac, skeletal muscle, and smooth muscle-we sought to identify the cell type(s) of action for a broad group of well-curated monogenic muscle disease genes (Benarroch et al, 2020) (Table S6). We tested the subset of genes for each disease group (e.g., hereditary cardiomyopathies, motor neuron diseases) for enrichment in cell type-specific markers from our muscle tissues (FDR < 0.1) (Methods, Figure 4A).…”

Section: Genes From Monogenic Muscle Disease Groups Are Enriched In Distinct Subsets Of Myocyte and Non-myocyte Cells In Cardiac Skeletalmentioning

confidence: 99%

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Single-nucleus cross-tissue molecular reference maps to decipher disease gene function

Eraslan

Drokhlyansky

Anand

et al. 2021

Preprint

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Understanding the function of genes and their regulation in tissue homeostasis and disease requires knowing the cellular context in which genes are expressed in tissues across the body. Single cell genomics allows the generation of detailed cellular atlases in human tissues, but most efforts are focused on single tissue types. Here, we establish a framework for profiling multiple tissues across the human body at single-cell resolution using single nucleus RNA-Seq (snRNA-seq), and apply it to 8 diverse, archived, frozen tissue types (three donors per tissue). We apply four snRNA-seq methods to each of 25 samples from 16 donors, generating a cross-tissue atlas of 209,126 nuclei profiles, and benchmark them vs. scRNA-seq of comparable fresh tissues. We use a conditional variational autoencoder (cVAE) to integrate an atlas across tissues, donors, and laboratory methods. We highlight shared and tissue-specific features of tissue-resident immune cells, identifying tissue-restricted and non-restricted resident myeloid populations. These include a cross-tissue conserved dichotomy between LYVE1- and HLA class II-expressing macrophages, and the broad presence of LAM-like macrophages across healthy tissues that is also observed in disease. For rare, monogenic muscle diseases, we identify cell types that likely underlie the neuromuscular, metabolic, and immune components of these diseases, and biological processes involved in their pathology. For common complex diseases and traits analyzed by GWAS, we identify the cell types and gene modules that potentially underlie disease mechanisms. The experimental and analytical frameworks we describe will enable the generation of large-scale studies of how cellular and molecular processes vary across individuals and populations.

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Section: Discussionmentioning

confidence: 73%

Section: Genes From Monogenic Muscle Disease Groups Are Enriched In Distinct Subsets Of Myocyte and Non-myocyte Cells In Cardiac Skeletalmentioning

confidence: 99%

Single-nucleus cross-tissue molecular reference maps to decipher disease gene function

Eraslan

Drokhlyansky

Anand

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Induced ER stress, including increased PERK signaling, was observed in skeletal muscle biopsy samples from myotonic dystrophy 1 patients and in mdx mice, a model of Duchenne muscular dystrophy (Hulmi et al, 2016; Ikezoe et al, 2007). Moreover, mutations in genes coding for aminoacyl-tRNA synthetases are implicated in human neuromuscular disorders (Benarroch et al, 2020), and autoantibodies against aminoacyl-tRNA synthetases are found in autoimmune disease (Targoff et al, 1993). Collectively, downstream genes of hnRNPK are strongly associated with neuromuscular and other disorders in humans, suggesting that targeting hnRNPK to regulate the expression of these genes and signaling may become a new therapeutic strategy for human diseases.…”

Section: Discussionmentioning

confidence: 99%

Myoparr-associated and -independent multiple roles of heterogeneous nuclear ribonucleoprotein K during skeletal muscle cell differentiation

Hitachi

Kiyofuji

Nakatani

et al. 2021

Preprint

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RNA-binding proteins (RBPs) regulate cell physiology via the formation of ribonucleic-protein complexes with coding and non-coding RNAs. RBPs have multiple functions in the same cells; however, the precise mechanism through which their pleiotropic functions are determined remains unknown. In this study, we revealed the multiple inhibitory functions of hnRNPK for myogenic differentiation. We first identified hnRNPK as a lncRNA Myoparr binding protein. Gain- and loss-of-function experiments showed that hnRNPK repressed the expression of myogenin at the transcriptional level via binding to Myoparr. Moreover, hnRNPK repressed the expression of a set of genes coding for aminoacyl-tRNA synthetases in a Myoparr-independent manner. Mechanistically, hnRNPK regulated the eIF2α/Atf4 pathway, one branch of the intrinsic pathways of the endoplasmic reticulum sensors, in differentiating myoblasts. Thus, our findings demonstrate that hnRNPK plays multiple lncRNA-dependent and -independent roles in the inhibition of myogenic differentiation, indicating that the analysis of lncRNA-binding proteins will be useful for elucidating both the physiological functions of lncRNAs and the multiple functions of RBPs.

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“…Motor neuron disease (MND) represents a wide and expanding group of different neurological disorders resulting from isolated or combined involvement of lower and upper motor neurons. The main adult-onset clinical disorder in this group is amyotrophic lateral sclerosis (ALS) 1 , however there is a high number of sporadic and hereditary neurological diseases that may present with MND phenotype and should be considered in the differential diagnosis (Table 1) 2,3,4 .…”

Section: Introductionmentioning

confidence: 99%

Adult-onset non-5q proximal spinal muscular atrophy: a comprehensive review

Pinto

Souza

Badia

et al. 2021

Arq. Neuro-Psiquiatr.

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Background: Adult-onset spinal muscular atrophy (SMA) represents an expanding group of inherited neurodegenerative disorders in clinical practice. Objective: This review aims to synthesize the main clinical, genetic, radiological, biochemical, and neurophysiological aspects related to the classical and recently described forms of proximal SMA. Methods: The authors performed a non-systematic critical review summarizing adult-onset proximal SMA presentations. Results: Previously limited to cases of SMN1-related SMA type 4 (adult form), this group has now more than 15 different clinical conditions that have in common the symmetrical and progressive compromise of lower motor neurons starting in adulthood or elderly stage. New clinical and genetic subtypes of adult-onset proximal SMA have been recognized and are currently target of wide neuroradiological, pathological, and genetic studies. Conclusions: This new complex group of rare disorders typically present with lower motor neuron disease in association with other neurological or systemic signs of impairment, which are relatively specific and typical for each genetic subtype.

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The 2021 version of the gene table of neuromuscular disorders (nuclear genome)

Cited by 53 publications

References 0 publications

Single-nucleus cross-tissue molecular reference maps to decipher disease gene function

Single-nucleus cross-tissue molecular reference maps to decipher disease gene function

Myoparr-associated and -independent multiple roles of heterogeneous nuclear ribonucleoprotein K during skeletal muscle cell differentiation

Adult-onset non-5q proximal spinal muscular atrophy: a comprehensive review

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