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  1. Article ; Online: Joint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids.

    Noack, Florian / Vangelisti, Silvia / Ditzer, Nora / Chong, Faye / Albert, Mareike / Bonev, Boyan

    Nature cell biology

    2023  Volume 25, Issue 12, Page(s) 1873–1883

    Abstract: Gene expression is regulated by multiple epigenetic mechanisms, which are coordinated in development and disease. However, current multiomics methods are frequently limited to one or two modalities at a time, making it challenging to obtain a ... ...

    Abstract Gene expression is regulated by multiple epigenetic mechanisms, which are coordinated in development and disease. However, current multiomics methods are frequently limited to one or two modalities at a time, making it challenging to obtain a comprehensive gene regulatory signature. Here, we describe a method-3D genome, RNA, accessibility and methylation sequencing (3DRAM-seq)-that simultaneously interrogates spatial genome organization, chromatin accessibility and DNA methylation genome-wide and at high resolution. We combine 3DRAM-seq with immunoFACS and RNA sequencing in cortical organoids to map the cell-type-specific regulatory landscape of human neural development across multiple epigenetic layers. Finally, we apply a massively parallel reporter assay to profile cell-type-specific enhancer activity in organoids and to functionally assess the role of key transcription factors for human enhancer activation and function. More broadly, 3DRAM-seq can be used to profile the multimodal epigenetic landscape in rare cell types and different tissues.
    MeSH term(s) Humans ; Epigenome ; Chromatin/genetics ; Chromatin/metabolism ; Epigenesis, Genetic ; DNA Methylation/genetics ; Organoids/metabolism
    Chemical Substances Chromatin
    Language English
    Publishing date 2023-11-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/s41556-023-01296-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5169: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 12: Show issues

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  2. Article ; Online: Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler.

    Noack, Florian / Vangelisti, Silvia / Raffl, Gerald / Carido, Madalena / Diwakar, Jeisimhan / Chong, Faye / Bonev, Boyan

    Nature neuroscience

    2022  Volume 25, Issue 2, Page(s) 154–167

    Abstract: How multiple epigenetic layers and transcription factors (TFs) interact to facilitate brain development is largely unknown. Here, to systematically map the regulatory landscape of neural differentiation in the mouse neocortex, we profiled gene expression ...

    Abstract How multiple epigenetic layers and transcription factors (TFs) interact to facilitate brain development is largely unknown. Here, to systematically map the regulatory landscape of neural differentiation in the mouse neocortex, we profiled gene expression and chromatin accessibility in single cells and integrated these data with measurements of enhancer activity, DNA methylation and three-dimensional genome architecture in purified cell populations. This allowed us to identify thousands of new enhancers, their predicted target genes and the temporal relationships between enhancer activation, epigenome remodeling and gene expression. We characterize specific neuronal transcription factors associated with extensive and frequently coordinated changes across multiple epigenetic modalities. In addition, we functionally demonstrate a new role for Neurog2 in directly mediating enhancer activity, DNA demethylation, increasing chromatin accessibility and facilitating chromatin looping in vivo. Our work provides a global view of the gene regulatory logic of lineage specification in the cerebral cortex.
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Chromatin ; DNA Methylation/genetics ; Enhancer Elements, Genetic/genetics ; Epigenome ; Gene Expression Regulation, Developmental/genetics ; Mice ; Nerve Tissue Proteins/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Basic Helix-Loop-Helix Transcription Factors ; Chromatin ; Nerve Tissue Proteins ; Neurog2 protein, mouse ; Transcription Factors
    Language English
    Publishing date 2022-02-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/s41593-021-01002-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4891: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 67: Show issues

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  3. Article ; Online: lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation.

    Delás, M Joaquina / Jackson, Benjamin T / Kovacevic, Tatjana / Vangelisti, Silvia / Munera Maravilla, Ester / Wild, Sophia A / Stork, Eva Maria / Erard, Nicolas / Knott, Simon R V / Hannon, Gregory J

    Cell reports

    2019  Volume 27, Issue 3, Page(s) 719–729.e6

    Abstract: Long non-coding RNAs (lncRNAs) show patterns of tissue- and cell type-specific expression that are very similar to those of protein coding genes and consequently have the potential to control stem and progenitor cell fate decisions along a ... ...

    Abstract Long non-coding RNAs (lncRNAs) show patterns of tissue- and cell type-specific expression that are very similar to those of protein coding genes and consequently have the potential to control stem and progenitor cell fate decisions along a differentiation trajectory. To understand the roles that lncRNAs may play in hematopoiesis, we selected a subset of mouse lncRNAs with potentially relevant expression patterns and refined our candidate list using evidence of conserved expression in human blood lineages. For each candidate, we assessed its possible role in hematopoietic differentiation in vivo using competitive transplantation. Our studies identified two lncRNAs that were required for hematopoiesis. One of these, Spehd, showed defective multilineage differentiation, and its silencing yielded common myeloid progenitors that are deficient in their oxidative phosphorylation pathway. This effort not only suggests that lncRNAs can contribute to differentiation decisions during hematopoiesis but also provides a path toward the identification of functional lncRNAs in other differentiation hierarchies.
    MeSH term(s) Animals ; Bone Marrow Transplantation ; Cell Differentiation ; Cell Line, Tumor ; Cell Lineage ; Cyclin-Dependent Kinase 6/genetics ; Cyclin-Dependent Kinase 6/metabolism ; Female ; GATA2 Transcription Factor/genetics ; GATA2 Transcription Factor/metabolism ; Hematopoiesis ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Mice ; Mice, Inbred C57BL ; Oxidative Phosphorylation ; Proto-Oncogene Proteins/antagonists & inhibitors ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; RNA Interference ; RNA, Long Noncoding/antagonists & inhibitors ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA, Small Interfering/metabolism ; Regeneration ; Trans-Activators/antagonists & inhibitors ; Trans-Activators/genetics ; Trans-Activators/metabolism
    Chemical Substances Ebf1 protein, mouse ; GATA2 Transcription Factor ; Gata2 protein, mouse ; Proto-Oncogene Proteins ; RNA, Long Noncoding ; RNA, Small Interfering ; Trans-Activators ; proto-oncogene protein Spi-1 ; Cdk6 protein, mouse (EC 2.7.11.22) ; Cyclin-Dependent Kinase 6 (EC 2.7.11.22)
    Language English
    Publishing date 2019-04-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2019.03.080
    Database MEDical Literature Analysis and Retrieval System OnLINE

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