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  1. Article ; Online: SoxC transcription factors shape the epigenetic landscape to establish competence for sensory differentiation in the mammalian organ of Corti.

    Wang, Xizi / Llamas, Juan / Trecek, Talon / Shi, Tuo / Tao, Litao / Makmura, Welly / Crump, J Gage / Segil, Neil / Gnedeva, Ksenia

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 34, Page(s) e2301301120

    Abstract: The auditory organ of Corti is comprised of only two major cell types-the mechanosensory hair cells and their associated supporting cells-both specified from a single pool of prosensory progenitors in the cochlear duct. Here, we show that competence to ... ...

    Abstract The auditory organ of Corti is comprised of only two major cell types-the mechanosensory hair cells and their associated supporting cells-both specified from a single pool of prosensory progenitors in the cochlear duct. Here, we show that competence to respond to Atoh1, a transcriptional master regulator necessary and sufficient for induction of mechanosensory hair cells, is established in the prosensory progenitors between E12.0 and 13.5. The transition to the competent state is rapid and is associated with extensive remodeling of the epigenetic landscape controlled by the SoxC group of transcription factors. Conditional loss of
    MeSH term(s) Animals ; SOXC Transcription Factors/genetics ; SOXC Transcription Factors/metabolism ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cochlea/metabolism ; Hair Cells, Auditory/metabolism ; Cell Differentiation ; Transcription Factors/metabolism ; Epigenesis, Genetic ; Organ of Corti ; Gene Expression Regulation, Developmental ; Mammals/metabolism
    Chemical Substances SOXC Transcription Factors ; Basic Helix-Loop-Helix Transcription Factors ; Transcription Factors
    Language English
    Publishing date 2023-08-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2301301120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: POU4F3 pioneer activity enables ATOH1 to drive diverse mechanoreceptor differentiation through a feed-forward epigenetic mechanism.

    Yu, Haoze V / Tao, Litao / Llamas, Juan / Wang, Xizi / Nguyen, John D / Trecek, Talon / Segil, Neil

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 29

    Abstract: During embryonic development, hierarchical cascades of transcription factors interact with lineage-specific chromatin structures to control the sequential steps in the differentiation of specialized cell types. While examples of transcription factor ... ...

    Abstract During embryonic development, hierarchical cascades of transcription factors interact with lineage-specific chromatin structures to control the sequential steps in the differentiation of specialized cell types. While examples of transcription factor cascades have been well documented, the mechanisms underlying developmental changes in accessibility of cell type-specific enhancers remain poorly understood. Here, we show that the transcriptional "master regulator" ATOH1-which is necessary for the differentiation of two distinct mechanoreceptor cell types, hair cells in the inner ear and Merkel cells of the epidermis-is unable to access much of its target enhancer network in the progenitor populations of either cell type when it first appears, imposing a block to further differentiation. This block is overcome by a feed-forward mechanism in which ATOH1 first stimulates expression of POU4F3, which subsequently acts as a pioneer factor to provide access to closed ATOH1 enhancers, allowing hair cell and Merkel cell differentiation to proceed. Our analysis also indicates the presence of both shared and divergent ATOH1/POU4F3-dependent enhancer networks in hair cells and Merkel cells. These cells share a deep developmental lineage relationship, deriving from their common epidermal origin, and suggesting that this feed-forward mechanism preceded the evolutionary divergence of these very different mechanoreceptive cell types.
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cell Differentiation ; Cochlea/metabolism ; Enhancer Elements, Genetic ; Epigenesis, Genetic ; Hair Cells, Auditory/cytology ; Hair Cells, Auditory/metabolism ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; Mechanoreceptors/metabolism ; Merkel Cells/metabolism ; Mice ; Transcription Factor Brn-3C/genetics ; Transcription Factor Brn-3C/metabolism
    Chemical Substances Atoh1 protein, mouse ; Basic Helix-Loop-Helix Transcription Factors ; Homeodomain Proteins ; Pou4f3 protein, mouse ; Transcription Factor Brn-3C
    Language English
    Publishing date 2021-07-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2105137118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Enhancer decommissioning imposes an epigenetic barrier to sensory hair cell regeneration.

    Tao, Litao / Yu, Haoze V / Llamas, Juan / Trecek, Talon / Wang, Xizi / Stojanova, Zlatka / Groves, Andrew K / Segil, Neil

    Developmental cell

    2021  Volume 56, Issue 17, Page(s) 2471–2485.e5

    Abstract: Adult mammalian tissues such as heart, brain, retina, and the sensory structures of the inner ear do not effectively regenerate, although a latent capacity for regeneration exists at embryonic and perinatal times. We explored the epigenetic basis for ... ...

    Abstract Adult mammalian tissues such as heart, brain, retina, and the sensory structures of the inner ear do not effectively regenerate, although a latent capacity for regeneration exists at embryonic and perinatal times. We explored the epigenetic basis for this latent regenerative potential in the mouse inner ear and its rapid loss during maturation. In perinatal supporting cells, whose fate is maintained by Notch-mediated lateral inhibition, the hair cell enhancer network is epigenetically primed (H3K4me1) but silenced (active H3K27 de-acetylation and trimethylation). Blocking Notch signaling during the perinatal period of plasticity rapidly eliminates epigenetic silencing and allows supporting cells to transdifferentiate into hair cells. Importantly, H3K4me1 priming of the hair cell enhancers in supporting cells is removed during the first post-natal week, coinciding with the loss of transdifferentiation potential. We hypothesize that enhancer decommissioning during cochlear maturation contributes to the failure of hair cell regeneration in the mature organ of Corti.
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cell Differentiation/physiology ; Cell Transdifferentiation/genetics ; Cell Transdifferentiation/physiology ; Epigenesis, Genetic/genetics ; Epigenesis, Genetic/physiology ; Hair Cells, Auditory/cytology ; Hair Cells, Auditory/metabolism ; Mice, Transgenic ; Receptors, Notch/metabolism ; Regeneration/physiology ; Regulatory Sequences, Nucleic Acid/genetics
    Chemical Substances Basic Helix-Loop-Helix Transcription Factors ; Receptors, Notch
    Language English
    Publishing date 2021-07-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2021.07.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5742: 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 76: Show issues

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  4. Article ; Online: Organ of Corti size is governed by Yap/Tead-mediated progenitor self-renewal.

    Gnedeva, Ksenia / Wang, Xizi / McGovern, Melissa M / Barton, Matthew / Tao, Litao / Trecek, Talon / Monroe, Tanner O / Llamas, Juan / Makmura, Welly / Martin, James F / Groves, Andrew K / Warchol, Mark / Segil, Neil

    Proceedings of the National Academy of Sciences of the United States of America

    2020  Volume 117, Issue 24, Page(s) 13552–13561

    Abstract: Precise control of organ growth and patterning is executed through a balanced regulation of progenitor self-renewal and differentiation. In the auditory sensory epithelium-the organ of Corti-progenitor cells exit the cell cycle in a coordinated wave ... ...

    Abstract Precise control of organ growth and patterning is executed through a balanced regulation of progenitor self-renewal and differentiation. In the auditory sensory epithelium-the organ of Corti-progenitor cells exit the cell cycle in a coordinated wave between E12.5 and E14.5 before the initiation of sensory receptor cell differentiation, making it a unique system for studying the molecular mechanisms controlling the switch between proliferation and differentiation. Here we identify the Yap/Tead complex as a key regulator of the self-renewal gene network in organ of Corti progenitor cells. We show that Tead transcription factors bind directly to the putative regulatory elements of many stemness- and cell cycle-related genes. We also show that the Tead coactivator protein, Yap, is degraded specifically in the Sox2-positive domain of the cochlear duct, resulting in down-regulation of Tead gene targets. Further, conditional loss of the
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Cell Cycle ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Differentiation ; Cell Self Renewal ; Gene Expression Regulation, Developmental ; Hair Cells, Auditory ; Mice ; Organ of Corti/cytology ; Organ of Corti/embryology ; Organ of Corti/metabolism ; Protein Binding ; SOXB1 Transcription Factors/genetics ; SOXB1 Transcription Factors/metabolism ; Stem Cells/cytology ; Stem Cells/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Adaptor Proteins, Signal Transducing ; Cell Cycle Proteins ; SOXB1 Transcription Factors ; Sox2 protein, mouse ; Transcription Factors ; Yap1 protein, mouse
    Language English
    Publishing date 2020-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2000175117
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Generation of inner ear hair cells by direct lineage conversion of primary somatic cells.

    Menendez, Louise / Trecek, Talon / Gopalakrishnan, Suhasni / Tao, Litao / Markowitz, Alexander L / Yu, Haoze V / Wang, Xizi / Llamas, Juan / Huang, Chichou / Lee, James / Kalluri, Radha / Ichida, Justin / Segil, Neil

    eLife

    2020  Volume 9

    Abstract: The mechanoreceptive sensory hair cells in the inner ear are selectively vulnerable to numerous genetic and environmental insults. In mammals, hair cells lack regenerative capacity, and their death leads to permanent hearing loss and vestibular ... ...

    Abstract The mechanoreceptive sensory hair cells in the inner ear are selectively vulnerable to numerous genetic and environmental insults. In mammals, hair cells lack regenerative capacity, and their death leads to permanent hearing loss and vestibular dysfunction. Their paucity and inaccessibility has limited the search for otoprotective and regenerative strategies. Growing hair cells in vitro would provide a route to overcome this experimental bottleneck. We report a combination of four transcription factors (
    MeSH term(s) Animals ; Cell Lineage ; Fibroblasts/physiology ; Hair Cells, Auditory, Inner/physiology ; Labyrinth Supporting Cells/physiology ; Mice/physiology ; Mice, Transgenic ; Tail ; Transcription Factors/metabolism
    Chemical Substances Transcription Factors
    Keywords covid19
    Language English
    Publishing date 2020-06-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.55249
    Database MEDical Literature Analysis and Retrieval System OnLINE

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