Chromatin and Nuclear Architecture in Stem Cells
2020; Elsevier BV; Volume: 15; Issue: 6 Linguagem: Inglês
10.1016/j.stemcr.2020.11.012
ISSN2213-6711
Autores Tópico(s)Pluripotent Stem Cells Research
ResumoHere we outline the contents of Stem Cell Reports' first special issue, on chromatin and nuclear architecture in stem cells. It features both reviews and original research articles, covering emerging topics in nuclear architecture including 3D genome organization in stem cells and early development, membraneless organelles, epigenetics-related therapy, and more. Here we outline the contents of Stem Cell Reports' first special issue, on chromatin and nuclear architecture in stem cells. It features both reviews and original research articles, covering emerging topics in nuclear architecture including 3D genome organization in stem cells and early development, membraneless organelles, epigenetics-related therapy, and more. DNA in living cells is wrapped around a core of histone proteins, which, together with additional structural proteins, comprise the fundamental repeating unit of life, chromatin (Kornberg, 1974Kornberg R.D. Chromatin structure: a repeating unit of histones and DNA.Science. 1974; 184: 868-871Crossref PubMed Scopus (1499) Google Scholar). The term "chromatin" was coined in 1882 by Walther Flemming "for the time being" to designate "that substance, in the nucleus, which upon treatment with dyes known as nuclear stains does absorb the dye." In other words, Flemming found a novel method to stain structures within the nucleus, and, for a lack of a better word (or understanding of what he was observing at the time), he named it "the stainable substance of the nucleus." This coloring technique was the basis of his influential book Zellsubstanz, Kern und Zelltheilung (Cell Substance, Nucleus and Cell Division) (Flemming, 1882Flemming W. Zellsubstanz, kern und zelltheilung. F. C. W. Vogel, 1882Crossref Google Scholar; Paweletz, 2001Paweletz N. Walther Flemming: pioneer of mitosis research.Nat. Rev. Mol. Cell Biol. 2001; 2: 72-75Crossref PubMed Scopus (89) Google Scholar). In this book he also coined the term "mitosis," and described its various stages in immaculate detail (Figures 1A–1C). Almost 50 years later, in 1929, Emil Heitz, using improved cytological staining techniques that he himself developed, suggested that chromatin is in fact divided into condensed and less active regions largely devoid of genes, which he termed "heterochromatin," and gene-rich domains, which he named "euchromatin" (Figures 1D) (Heitz, 1929Heitz E. Heterochromatin, Chromocentren, Chromomeren.Ber. Dtsch. Bot. Ges. 1929; 47: 274-284Google Scholar). Despite being over-simplistic, these terms are extremely useful, and are extensively used to explain chromatin structure and regulation. Essentially all cellular processes are governed by changes in chromatin structure, which, in turn, regulate gene expression. Such changes are particularly pertinent in stem cells, which maintain potency but undergo massive changes upon differentiation (Lim and Meshorer, 2020Lim P.S.L. Meshorer E. Organization of the Pluripotent Genome.Cold Spring Harb. Perspect. Biol. 2020; : a040204PubMed Google Scholar). In recent years, our understanding of chromatin and nuclear architecture has increased considerably, owing to the development of new microscopes and cutting-edge imaging-based methods, breaking the limit of diffraction, and to high-throughput sequencing-based technologies, e.g., Hi-C, designed to capture genome organization in three dimensions. Combined with CRISPR-based techniques, the possibilities become essentially endless, from endogenous labeling of nuclear structures, to CRISPR-based screens for epigenetic and nuclear modifiers, and much more. This special issue of Stem Cell Reports, dedicated to chromatin and nuclear architecture in stem cells, features both original research papers and several review articles, the latter covering chromatin and epigenetic regulation in early mammalian embryogenesis (Xia and Xie, 2020Xia W. Xie W. Rebooting the epigenomes during mammalian early embryogenesis.Stem Cell Reports. 2020; 15 (this issue): 1158-1175Abstract Full Text Full Text PDF Scopus (7) Google Scholar), three-dimensional organization of the pluripotent genome (Pelham-Webb et al., 2020Pelham-Webb B. Murphy D. Apostolou E. Dynamic 3D chromatin reorganization during establishment and maintenance of pluripotency.Stem Cell Reports. 2020; 15 (this issue): 1176-1195Abstract Full Text Full Text PDF Scopus (3) Google Scholar), nucleolar function and organization in pluripotent cells (Gupta and Santoro, 2020Gupta S. Santoro R. Regulation and roles of the nucleolus in embryonic stem cells: from ribosome biogenesis to genome organization.Stem Cell Reports. 2020; 15 (this issue): 1206-1219Abstract Full Text Full Text PDF Scopus (3) Google Scholar), chromatin-associated membraneless organelles in pluripotency (Grosch et al., 2020Grosch M. Ittermann S. Shaposhnikov D. Drukker M. Chromatin associated membraneless organelles in regulation of cellular differentiation.Stem Cell Reports. 2020; 15 (this issue): 1220-1232Abstract Full Text Full Text PDF Scopus (1) Google Scholar), and finally, clinical implications of the epigenetic landscape and histone modifications in stem cells (Völker-Albert et al., 2020Völker-Albert M. Bronkhorst A. Holdenrieder S. Imhof A. Histone modifications in stem cell development and their clinical implications.Stem Cell Reports. 2020; 15 (this issue): 1196-1205Abstract Full Text Full Text PDF Scopus (2) Google Scholar). The primary research papers included in this special issue contain method development, where the authors describe a single mammalian locus isolation technique using TALEs (Knaupp et al., 2020Knaupp A.S. Mohenska M. Larcombe M.R. Ford E. Lim S.M. Wong K. Chen J. Firas J. Huang C. Liu X. et al.TINC - a method to dissect regulatory complexes at single locus resolution - reveals numerous proteins at the Nanog promoter.Stem Cell Reports. 2020; 15 (this issue): 1246-1259Abstract Full Text Full Text PDF Scopus (1) Google Scholar), as well as several reports identifying chromatin/epigenetic modifiers regulating pluripotency, stem cell identity, or differentiation. Working with PRC2 mutant mouse embryonic stem cells (ESCs), Perino et al. reveal the functional differences in the recruitment of the PRC2 complexes to chromatin, demonstrating that PRC2.1 recruitment is dependent on MTF2, whereas PRC2.2 recruitment is mediated by PRC1 (Perino et al., 2020Perino M. van Mierlo G. Loh C. Wardle S.M.T. Zijlmans D.W. Marks H. Veenstra G.J.C. Two Functional Axes of Feedback-Enforced PRC2 Recruitment in Mouse Embryonic Stem Cells.Stem Cell Reports. 2020; 15 (this issue): 1287-1300Abstract Full Text Full Text PDF Scopus (3) Google Scholar). Another study, which focuses on heterochromatin regulation in mouse ESCs, identifies a role for MeCP2 in regulating both chromocenter clustering and the targeting of major satellite transcripts to pericentric heterochromatin (Fioriniello et al., 2020Fioriniello S. Csukonyi E. Marano D. Brancaccio A. Madonna M. Zarrillo C. Romano A. Marracino F. Matarazzo M.R. D'Esposito M. Della Ragione F. MeCP2 and major satellite forward RNA cooperate for pericentric heterochromatin organization.Stem Cell Reports. 2020; 15 (this issue): 1317-1332Abstract Full Text Full Text PDF Scopus (5) Google Scholar). Vidal et al. show that histone lysine 9 (H3K9) methylation in euchromatic regions, and especially the histone methyltransferase EHMT1, plays essential roles during reprogramming to pluripotency (Vidal et al., 2020Vidal S.E. Polyzos A. Chatterjee K. Ee L.S. Swanzey E. Morales-Valencia J. Wang H. Parikh C.N. Amlani B. Tu S. et al.Context-dependent requirement of euchromatic histone methyltransferase activity during reprogramming to pluripotency.Stem Cell Reports. 2020; 15 (this issue): 1233-1245Abstract Full Text Full Text PDF Scopus (1) Google Scholar). Analyzing the binding partners of a previously identified pluripotency regulator, SET, Harikumar et al. identify the Wnt and p53 pathways as mediators of SET's function in mouse ESCs (Harikumar et al., 2020Harikumar A. Lim P.S.L. Nissim-Rafinia M. Park J.E. Sze S.K. Meshorer E. Embryonic stem cell differentiation is regulated by SET through interactions with p53 and β-catenin.Stem Cell Reports. 2020; 15 (this issue): 1260-1274Abstract Full Text Full Text PDF Scopus (2) Google Scholar). Another study explores the regulation of the trophoblast stem cell state by TET1 and 5-hydroxymethylation (Senner et al., 2020Senner C.E. Chrysanthou S. Burge S. Lin H.Y. Branco M.R. Hemberger M. TET1 and 5-hydroxymethylation preserve the stem cell state of mouse trophoblast.Stem Cell Reports. 2020; 15 (this issue): 1301-1316Abstract Full Text Full Text PDF Scopus (2) Google Scholar). Finally, reanalyzing a CRISPR screen conducted in human ESCs aimed at identifying genes important for ESCs, Lezmi et al. identify the chromatin regulator ZMYM2, which restricts human ESCs growth on the one hand, but is essential for teratoma formation on the other (Lezmi et al., 2020Lezmi E. Weissbein U. Golan-Lev T. Nissim-Rafinia M. Meshorer E. Benvenisty N. The chromatin regulator ZMYM2 restricts human pluripotent stem cell growth and is essential for teratoma formation.Stem Cell Reports. 2020; 15 (this issue): 1275-1286Abstract Full Text Full Text PDF Scopus (1) Google Scholar). This special issue on chromatin and nuclear architecture in stem cells is developed in parallel with an ISSCR digital series on the same topic, which brings together many of the authors from this issue and additional experts in the field for a discussion of these exciting themes. We as guest editors (Figure 2) would like to thank the authors for their contributions to this issue and Stem Cell Reports for featuring this important area of research. TINC— A Method to Dissect Regulatory Complexes at Single-Locus Resolution— Reveals an Extensive Protein Complex at the Nanog PromoterKnaupp et al.Stem Cell ReportsDecember 08, 2020In BriefHere, Knaupp and colleagues describe TINC, an epigenetic method that allows interrogation of mammalian regulatory complexes at a single-locus resolution. TINC was applied to dissect the transcriptional complex at the Nanog promoter in embryonic stem cells, revealing hundreds of interactors, including RCOR2, hence redefining how this gene is regulated in pluripotency. Full-Text PDF Open AccessTET1 and 5-Hydroxymethylation Preserve the Stem Cell State of Mouse TrophoblastSenner et al.Stem Cell ReportsMay 21, 2020In BriefTET1 and its conferred epigenetic modification 5-hydroxymethylation are critical for maintaining pluripotency of embryonic stem cells. In this article, Senner and colleagues describe in-depth the role of this modification, in conjunction with DNA methylation, in trophoblast stem cells, and determine a distinct role for TET1 in demarcating putative trophoblast enhancers and thereby establishing trophoblast-specific gene networks. Full-Text PDF Open AccessChromatin-Associated Membraneless Organelles in Regulation of Cellular DifferentiationGrosch et al.Stem Cell ReportsNovember 19, 2020In BriefIn this review, Drukker and colleagues describe emerging roles of nuclear membraneless organelles in chromatin and how they affect development. Based on studies of stem cells, they describe primarily the roles of a key form of membraneless organelles, named paraspeckles, and the roles that lncRNAs might play in the phase separation of membraneless organelles in the chromatin during development. Full-Text PDF Open AccessThe Chromatin Regulator ZMYM2 Restricts Human Pluripotent Stem Cell Growth and Is Essential for Teratoma FormationLezmi et al.Stem Cell ReportsJune 18, 2020In BriefIn this article Lezmi et al. identified the chromatin regulator, ZMYM2, as a major epigenetic factor involved in human ESCs growth, and showed that its loss causes adverse transcriptional and epigenetic changes. ZMYM2-null ESCs overexpress naive pluripotency genes while losing their capacity to properly differentiate in vitro and form teratomas in vivo. Full-Text PDF Open AccessDynamic 3D Chromatin Reorganization during Establishment and Maintenance of PluripotencyPelham-Webb et al.Stem Cell ReportsNovember 25, 2020In BriefIn this review article, Apostolou and colleagues discuss how the unique 3D chromatin architecture of pluripotent stem cells is established during somatic cell reprogramming and maintained during self-renewal. They analyze progress and gaps in our knowledge regarding the driving forces of 3D chromatin reorganization, the links to transcriptional changes and the impact on cell fate decisions. Full-Text PDF Open AccessHistone Modifications in Stem Cell Development and Their Clinical ImplicationsVölker-Albert et al.Stem Cell ReportsDecember 08, 2020In BriefIn this article, Axel Imhof and colleagues discuss recent findings on the role of histone modifications in stem cell regulation. In particular, this article focuses on the effects of global processes such as the cell cycle or the metabolic state on chromatin maturation and links them to targeted therapeutic interventions aiming to reset the epigenetic landscape. Full-Text PDF Open AccessRegulation and Roles of the Nucleolus in Embryonic Stem Cells: From Ribosome Biogenesis to Genome OrganizationGupta et al.Stem Cell ReportsSeptember 24, 2020In BriefIn this review article, Santoro and colleague describe the regulation and role of the largest subnuclear compartment of the cell, the nucleolus, in embryonic stem cells (ESCs). Specifically, the authors highlight recent findings describing how the hyperactive transcriptional state and open chromatin structure of ribosomal RNA genes, which are located in the nucleolus, are regulated and affect ribosome biogenesis activities and genome organization in ESCs and during differentiation. Full-Text PDF Open AccessTwo Functional Axes of Feedback-Enforced PRC2 Recruitment in Mouse Embryonic Stem CellsPerino et al.Stem Cell ReportsAugust 6, 2020In BriefVeenstra and Marks and colleagues systematically analyze the contributions of Polycomb Repressive Complexes PRC2.1, PRC2.2, and PRC1 in ESCs, using null mutations in combination with chemical inhibition of EED, the core subunit that interacts with H3K27me3. The mutations and the EED inhibition uncover the functional overlap, and the compensatory and highly interdependent binding of PRC2.1, PRC2.2, and PRC1. Full-Text PDF Open AccessMeCP2 and Major Satellite Forward RNA Cooperate for Pericentric Heterochromatin OrganizationFioriniello et al.Stem Cell ReportsDecember 08, 2020In BriefDella Ragione and colleagues describe a novel function of MeCP2 and MajSat forward transcript in terms of their reciprocal targeting to chromocenters in neurons through their physical interaction. Moreover, MeCP2B has a prominent role in higher-order PCH organization, with both its MBD and TRD involved in this process. These findings further clarify MeCP2 function in the regulation of chromatin architecture. Full-Text PDF Open AccessEmbryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-CateninHarikumar et al.Stem Cell ReportsDecember 08, 2020In BriefPreviously, Meshorer and colleagues identified the rapid downregulation of SETα following ESC differentiation. This study reveals that interaction of SET with P53 contributes to defects in lineage marker expression observed in SET-KO ESCs. Paradoxically, although canonical Wnt signaling is activated in the absence of SET, lower levels of active β-catenin are observed, suggesting a SET-mediated redistribution of nuclear β-catenin. Full-Text PDF Open AccessRebooting the Epigenomes during Mammalian Early EmbryogenesisXia et al.Stem Cell ReportsOctober 8, 2020In BriefIn this review article, Xie and Xia discuss the recent progress for understanding the dynamics and functions of epigenetic reprogramming in early mammalian development. Particularly, the authors summarize distinct fates and functions of the parental epigenomes during early mammalian development, and highlight the "primitive" chromatin state prior to zygotic genome activation that connects the parental epigenomes to the embryonic epigenome. Full-Text PDF Open Access
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