LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription

Scionti, Isabella; Hayashi, Shinichiro; Mouradian, Sandrine; Girard, Emmanuelle; Lima, Joana Esteves de; Morel, Véronique; Simonet, Thomas; Wurmser, Maud; Maire, Pascal; Ancelin, Katia; Metzger, Eric; Schüle, Roland; Goillot, Evelyne; Relaix, Frédéric; Schaeffer, Laurent

doi:10.1016/j.celrep.2017.01.078

Cited by 49 publications

(76 citation statements)

References 48 publications

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“…In injured muscles, increased glycolysis may generate the glycolytic intermediates necessary for the production of new biomass and metabolites utilized by histone-and DNA-modifying enzymes whereas oxidative phosphorylation would generate the ATP required for MuSC proliferation (Ryall et al, 2015a;Pala et al, 2018). Indeed, metabolites generated by different metabolic pathways regulate the activity of chromatin-modifying enzymes known to control different aspects of MuSC biology (McKinnell et al, 2008;Juan et al, 2011;Kawabe et al, 2012;Liu et al, 2013;Ryall et al, 2015b;Boonsanay et al, 2016;Faralli et al, 2016;Scionti et al, 2017;Das et al, 2017;Tosic et al, 2018;Puri and Mercola, 2012). For instance, the oscillation of intermediary metabolites of the NAD biosynthetic pathways may be relevant for circadian gene expression in MuSCs and skeletal muscle (Nakahata et al, 2009;Ryall et al, 2015b;Solanas et al, 2017;Andrews et al, 2010;Lowe et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions

et al. 2019

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Dedicated stem cells ensure post-natal growth, repair, and homeostasis of skeletal muscle. Following injury, muscle stem cells (MuSCs) exit from quiescence and divide to reconstitute the stem cell pool and give rise to muscle progenitors. The transcriptomes of pooled MuSCs have provided a rich source of information for describing the genetic programs of distinct static cell states; however, bulk microarray and RNA-seq provide only averaged gene expression profiles, blurring the heterogeneity and developmental dynamics of asynchronous MuSC populations. Instead, the granularity required to identify distinct cell types, states, and their dynamics can be afforded by single-cell analysis. We were able to compare the transcriptomes of thousands of MuSCs and primary myoblasts isolated from homeostatic or regenerating muscles by single-cell RNA- sequencing. Using computational approaches, we could reconstruct dynamic trajectories and place, in a pseudotemporal manner, the transcriptomes of individual MuSC within these trajectories. This approach allowed for the identification of distinct clusters of MuSCs and primary myoblasts with partially overlapping but distinct transcriptional signatures, as well as the description of metabolic pathways associated with defined MuSC states.

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Section: Discussionmentioning

confidence: 99%

Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions

et al. 2019

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“…In brief, LSD1 was implicated in spermatogenesis [62,63] and adipogenesis [64,65], while its loss promoted differentiation of mesenchymal stem cells towards bone or liver [66][67][68][69][70][71]. In a different context, LSD1 was required by the satellite cells (stem cells of muscle) for myogenic regeneration after injury [72] or for proper myoblast differentiation [73].…”

Section: Lsd1 In Other Normal Stem Cell Typesmentioning

confidence: 99%

LSD1/KDM1A, a Gate-Keeper of Cancer Stemness and a Promising Therapeutic Target

Karakaidos

Verigos

Magklara

2019

Cancers

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A new exciting area in cancer research is the study of cancer stem cells (CSCs) and the translational implications for putative epigenetic therapies targeted against them. Accumulating evidence of the effects of epigenetic modulating agents has revealed their dramatic consequences on cellular reprogramming and, particularly, reversing cancer stemness characteristics, such as self-renewal and chemoresistance. Lysine specific demethylase 1 (LSD1/KDM1A) plays a well-established role in the normal hematopoietic and neuronal stem cells. Overexpression of LSD1 has been documented in a variety of cancers, where the enzyme is, usually, associated with the more aggressive types of the disease. Interestingly, recent studies have implicated LSD1 in the regulation of the pool of CSCs in different leukemias and solid tumors. However, the precise mechanisms that LSD1 uses to mediate its effects on cancer stemness are largely unknown. Herein, we review the literature on LSD1’s role in normal and cancer stem cells, highlighting the analogies of its mode of action in the two biological settings. Given its potential as a pharmacological target, we, also, discuss current advances in the design of novel therapeutic regimes in cancer that incorporate LSD1 inhibitors, as well as their future perspectives.

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“…In other cases, however it has been shown that Lsd1 is involved in demethylation of H3K9 or H4K20 and can act as a transcriptional co-activator (15)(16)(17)(18). Loss of Lsd1 in all cells leads to early lethality in mice (15), whereas tissue specific manipulations of Lsd1 function revealed roles in the development and homeostasis of several organs and cell types (15,(19)(20)(21)(22)(23)(24)(25)(26)(27). Lsd1 has been shown to be particularly important in the nervous system where it regulates neurogenesis at several levels.…”

Section: Introductionmentioning

confidence: 99%

Histone demethylase Lsd1 is required for the differentiation of neural cells in the cnidarianNematostella vectensis

Gahan

Kouzel

Rentzsch

2020

Preprint

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The evolution of multicellularity was accompanied by the emergence of processes to regulate cell fate, identity and differentiation in a robust and faithful manner. Chromatin regulation has emerged as a key process in development and yet its contribution to the evolution of such processes is largely unexplored. Chromatin is regulated by a diverse set of proteins, which themselves are tightly regulated in order to play cell/ tissue-specific functions. Using the cnidarian Nematostella vectensis, a model for basal metazoans, we explore the function of one such chromatin regulator, Lysine specific demethylase 1 (Lsd1). We generated an endogenously tagged allele and show that the expression of NvLsd1 is developmentally regulated and higher in differentiated neural cells than their progenitors. We further show, using a CRISPR/Cas9 generated mutant that loss of NvLsd1 leads to several distinct developmental abnormalities. Strikingly, NvLsd1 loss leads to the almost complete loss of differentiated cnidocytes, cnidarian-specific neural cells, which we show to be the result of a cell-autonomous requirement for NvLsd1. Together this suggests that complex regulation of developmental processes by chromatin modifying proteins predates the split of the cnidarian and bilaterian lineages, approximately 600 million years ago, and may constitute an ancient feature of animal development.

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LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription

Cited by 49 publications

References 48 publications

Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions

Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions

LSD1/KDM1A, a Gate-Keeper of Cancer Stemness and a Promising Therapeutic Target

Histone demethylase Lsd1 is required for the differentiation of neural cells in the cnidarianNematostella vectensis

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