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  1. Article ; Online: G1-phase progression in pluripotent stem cells.

    Ter Huurne, Menno / Stunnenberg, Hendrik G

    Cellular and molecular life sciences : CMLS

    2021  Volume 78, Issue 10, Page(s) 4507–4519

    Abstract: During early embryonic development both the rapid increase in cell number and the expression of genes that control developmental decisions are tightly regulated. Accumulating evidence has indicated that these two seemingly independent processes are ... ...

    Abstract During early embryonic development both the rapid increase in cell number and the expression of genes that control developmental decisions are tightly regulated. Accumulating evidence has indicated that these two seemingly independent processes are mechanistically intertwined. The picture that emerges from studies on the cell cycle of embryonic stem cells is one in which proteins that promote cell cycle progression prevent differentiation and vice versa. Here, we review which transcription factors and signalling pathways play a role in both maintenance of pluripotency as well as cell cycle progression. We will not only describe the mechanism behind their function but also discuss the role of these regulators in different states of mouse pluripotency. Finally, we elaborate on how canonical cell cycle regulators impact on the molecular networks that control the maintenance of pluripotency and lineage specification.
    MeSH term(s) Animals ; Cell Differentiation/physiology ; Embryonic Stem Cells/physiology ; G1 Phase/physiology ; Humans ; Pluripotent Stem Cells/physiology ; Signal Transduction/physiology
    Language English
    Publishing date 2021-04-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-021-03797-8
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  2. Article ; Online: Brd4-independence in ground state pluripotency.

    Atlasi, Yaser / Stunnenberg, Hendrik G

    Nature cell biology

    2018  Volume 20, Issue 5, Page(s) 513–515

    MeSH term(s) Embryonic Stem Cells ; Nuclear Proteins ; Pluripotent Stem Cells ; Transcription Factors
    Chemical Substances Nuclear Proteins ; Transcription Factors
    Language English
    Publishing date 2018-05-09
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/s41556-018-0099-y
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  3. Article: Extensive patient-to-patient single nucleus transcriptome heterogeneity in pheochromocytomas and paragangliomas.

    Brazda, Peter / Ruiz-Moreno, Cristian / Megchelenbrink, Wout L / Timmers, Henri J L M / Stunnenberg, Hendrik G

    Frontiers in oncology

    2022  Volume 12, Page(s) 965168

    Abstract: Pheochromocytoma, neuroendocrine tumor, single cell RNA-sequencing, transcriptome, heterogeneity, SDHB, RET, paraganglinoma; Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors with varied genetic makeup and are associated with ... ...

    Abstract Pheochromocytoma, neuroendocrine tumor, single cell RNA-sequencing, transcriptome, heterogeneity, SDHB, RET, paraganglinoma; Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors with varied genetic makeup and are associated with high cardiovascular morbidity and a variable risk of malignancy. The source of the transcriptional heterogeneity of the disease and the underlying biological processes that determine the outcome of PCPG remain largely unclear. We focused on PCPG tumors with germline SDHB and RET mutations, which represent distinct prognostic groups with worse or better prognoses, respectively. We applied single-nuclei RNA sequencing (snRNA-seq) to tissue samples from 11 patients and found high patient-to-patient transcriptome heterogeneity in neuroendocrine tumor cells. The tumor microenvironment also showed heterogeneous profiles, mainly contributed by macrophages of the immune cell clusters and Schwann cells of the stroma. By performing non-negative matrix factorization, we identified common transcriptional programs active in RET and SDHB, as well as distinct modules, including neuronal development, hormone synthesis and secretion, and DNA replication. Similarities between the transcriptomes of the tumor cells and those of the chromaffin- and precursor cell types suggests different developmental stages at which PC and PG tumors appear to be arrested.
    Language English
    Publishing date 2022-08-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.965168
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  4. Article ; Online: The interplay of epigenetic marks during stem cell differentiation and development.

    Atlasi, Yaser / Stunnenberg, Hendrik G

    Nature reviews. Genetics

    2017  Volume 18, Issue 11, Page(s) 643–658

    Abstract: Chromatin, the template for epigenetic regulation, is a highly dynamic entity that is constantly reshaped during early development and differentiation. Epigenetic modification of chromatin provides the necessary plasticity for cells to respond to ... ...

    Abstract Chromatin, the template for epigenetic regulation, is a highly dynamic entity that is constantly reshaped during early development and differentiation. Epigenetic modification of chromatin provides the necessary plasticity for cells to respond to environmental and positional cues, and enables the maintenance of acquired information without changing the DNA sequence. The mechanisms involve, among others, chemical modifications of chromatin, changes in chromatin constituents and reconfiguration of chromatin interactions and 3D structure. New advances in genome-wide technologies have paved the way towards an integrative view of epigenome dynamics during cell state transitions, and recent findings in embryonic stem cells highlight how the interplay between different epigenetic layers reshapes the transcriptional landscape.
    MeSH term(s) Animals ; Cell Differentiation/physiology ; Chromatin/metabolism ; Chromatin Assembly and Disassembly/physiology ; Epigenesis, Genetic/physiology ; Genome-Wide Association Study ; Human Embryonic Stem Cells/cytology ; Human Embryonic Stem Cells/physiology ; Humans
    Chemical Substances Chromatin
    Language English
    Publishing date 2017-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2035157-4
    ISSN 1471-0064 ; 1471-0056
    ISSN (online) 1471-0064
    ISSN 1471-0056
    DOI 10.1038/nrg.2017.57
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  5. Article ; Online: Transcriptional and epigenetic control in mouse pluripotency: lessons from in vivo and in vitro studies.

    Habibi, Ehsan / Stunnenberg, Hendrik G

    Current opinion in genetics & development

    2017  Volume 46, Page(s) 114–122

    Abstract: Pluripotent cells were first derived from mouse blastocysts several decades ago. Since then, our knowledge of the molecular events that occur in the pre-implantation embryo has been vastly progressing. The emergence of epigenetics has revolutionized stem ...

    Abstract Pluripotent cells were first derived from mouse blastocysts several decades ago. Since then, our knowledge of the molecular events that occur in the pre-implantation embryo has been vastly progressing. The emergence of epigenetics has revolutionized stem cell and developmental biology and further deepened our understanding of the underlying molecular mechanisms controlling the early embryo development. In particular, the emergence of massive parallel sequencing technologies has opened new avenues and became indispensable tools in modern biology. Additionally, development of new and exciting techniques for genome manipulation (TALEN and CRISPR/Cas9) and in vivo imaging provide unique opportunities to perturb and trace biological systems at very high resolution. Finally, recent single-cell - omics combined with sophisticated computational methodologies allow accurate, quantitative measurements for deconvolution of cellular variation in complex cell populations. Collectively, these achievements enabled the detailed characterization and monitoring of various cell states and trajectories during early stages of embryonic development. Here we review recent studies of the transcriptional and epigenetic changes during very early stages of mouse embryo development and compare these with pluripotent cells grown in vitro under different culture conditions. We discuss whether the in vitro cell states have an 'epi-phenocopy' in the embryo and refine our understanding of the circuitries controlling pluripotency and lineage commitment during early stages of mouse development.
    Language English
    Publishing date 2017-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1077312-5
    ISSN 1879-0380 ; 0959-437X
    ISSN (online) 1879-0380
    ISSN 0959-437X
    DOI 10.1016/j.gde.2017.07.005
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  6. Article ; Online: I Remember You: Epigenetic Priming in Epithelial Stem Cells.

    Novakovic, Boris / Stunnenberg, Hendrik G

    Immunity

    2017  Volume 47, Issue 6, Page(s) 1019–1021

    Abstract: Exposure to inflammatory stimuli can remodel immune cells in a way that alters their response to future insults. In a landmark paper in Nature, Elaine Fuchs and colleagues show that memory of inflammation is not restricted to the hematopoietic lineage ( ... ...

    Abstract Exposure to inflammatory stimuli can remodel immune cells in a way that alters their response to future insults. In a landmark paper in Nature, Elaine Fuchs and colleagues show that memory of inflammation is not restricted to the hematopoietic lineage (Naik et al., 2017).
    MeSH term(s) Epigenesis, Genetic ; Epigenomics ; Humans ; Inflammation ; Skin ; Stem Cells
    Language English
    Publishing date 2017-12-20
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2017.12.005
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  7. Article ; Online: The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery.

    Stunnenberg, Hendrik G / Hirst, Martin

    Cell

    2017  Volume 167, Issue 5, Page(s) 1145–1149

    Abstract: The International Human Epigenome Consortium (IHEC) coordinates the generation of a catalog of high-resolution reference epigenomes of major primary human cell types. The studies now presented (see the Cell Press IHEC web portal at http://www.cell.com/ ... ...

    Abstract The International Human Epigenome Consortium (IHEC) coordinates the generation of a catalog of high-resolution reference epigenomes of major primary human cell types. The studies now presented (see the Cell Press IHEC web portal at http://www.cell.com/consortium/IHEC) highlight the coordinated achievements of IHEC teams to gather and interpret comprehensive epigenomic datasets to gain insights in the epigenetic control of cell states relevant for human health and disease. PAPERCLIP.
    MeSH term(s) DNA Methylation ; Databases, Genetic ; Disease/genetics ; Epigenesis, Genetic ; Epigenomics ; Genome, Human ; Histone Code ; Humans
    Language English
    Publishing date 2017-02-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2016.11.007
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  8. Article ; Online: Epigenetic memory: A macrophage perspective.

    Logie, Colin / Stunnenberg, Hendrik G

    Seminars in immunology

    2016  Volume 28, Issue 4, Page(s) 359–367

    Abstract: The molecular basis of cellular memory is a fascinating topic that progressed with great strides during the last few decades. In the case of cells of the immune system, cellular memory likely extends beyond cell fate determination mechanisms, since ... ...

    Abstract The molecular basis of cellular memory is a fascinating topic that progressed with great strides during the last few decades. In the case of cells of the immune system, cellular memory likely extends beyond cell fate determination mechanisms, since immunity can tailor its responses to a potentially hostile environment that is a priori variable if not unpredictable. One particularly versatile innate immune system cell type is the macrophage. These phagocytes occur in all organs and tissues as resident cells or as differentiation products of recruited circulating blood monocytes. They come in many flavours determined by the tissue of residence and by external factors such as microbes. Recently, macrophage epigenome profiling has revealed thousands of chromosomal loci that are differentially active in macrophages, revealing chromosome elements that drive macrophage gene expression. The most dynamic epigenomic mark is nucleosomal histone acetylation. This mark is found at gene promoters and enhancers and correlates very well with gene expression changes. A second mark is H3K4me3, which sharply decorates the promoters of most protein coding genes that are (potentially) expressed. H3K4me3 at promoters is surrounded by its precursor H3K4me1. However, most often H3K4me1 occurs without H3K4me3 at enhancers where it appears together with histone acetylation, but can persist long after acetylation decreased. Hence, the biochemical signal H3K4me1 embodies appears to be a key to the plasticity of macrophage gene expression potential.
    Language English
    Publishing date 2016-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1016/j.smim.2016.06.003
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  9. Article ; Online: Dynamic chromatin organization: Role in development and disease.

    Kuznetsova, Tatyana / Stunnenberg, Hendrik G

    The international journal of biochemistry & cell biology

    2016  Volume 76, Page(s) 119–122

    Abstract: The spatial organization of chromatin in the nucleus is important for proper regulation of gene expression. The cell-type specific transcription program is mainly controlled by distal regulatory elements, which can dynamically engage in long-range ... ...

    Abstract The spatial organization of chromatin in the nucleus is important for proper regulation of gene expression. The cell-type specific transcription program is mainly controlled by distal regulatory elements, which can dynamically engage in long-range interactions with their target genes. These long-range interactions mostly occur within insulated genomic domains and are constrained by global organization of the chromatin, providing an extra layer of regulation. Genetic alterations can lead to disruption of spatial organization and consequently aberrant gene expression. In this review we will discuss the multiple layers of chromatin organization, how this organization changes during development and how its disruption can lead do aberrant gene expression and disease.
    MeSH term(s) Animals ; Chromatin/genetics ; Chromatin/metabolism ; Chromatin/pathology ; Chromatin Assembly and Disassembly ; Humans
    Chemical Substances Chromatin
    Language English
    Publishing date 2016
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1228429-4
    ISSN 1878-5875 ; 1357-2725
    ISSN (online) 1878-5875
    ISSN 1357-2725
    DOI 10.1016/j.biocel.2016.05.006
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  10. Article ; Online: The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery.

    Stunnenberg, Hendrik G / Hirst, Martin

    Cell

    2016  Volume 167, Issue 7, Page(s) 1897

    Language English
    Publishing date 2016--15
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2016.12.002
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