LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Back to previous search Search history
Advanced search

Your last searches

  1. AU="Norrie, Jackie"
  2. AU="Kelly, J. M."

Search results

Result 1 - 7 of total 7

Search options

  1. Article: Identification of Evolutionarily Conserved VSX2 Enhancers in Retinal Development.

    Honnell, Victoria / Sweeney, Shannon / Norrie, Jackie / Ramirez, Cody / Xu, Beisi / Teubner, Brett / Lee, Ah Young / Bell, Claire / Dyer, Michael A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Super-enhancers (SEs) are expansive regions of genomic DNA that regulate the expression of genes involved in cell identity and cell fate. Recently, we found that distinct modules within a murine SE regulate gene expression of master regulatory ... ...

    Abstract Super-enhancers (SEs) are expansive regions of genomic DNA that regulate the expression of genes involved in cell identity and cell fate. Recently, we found that distinct modules within a murine SE regulate gene expression of master regulatory transcription factor
    Language English
    Publishing date 2023-10-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.17.562742
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article: Latent Epigenetic Programs in Müller Glia Contribute to Stress, Injury, and Disease Response in the Retina.

    Norrie, Jackie L / Lupo, Marybeth / Shirinifard, Abbas / Djekidel, Nadhir / Ramirez, Cody / Xu, Beisi / Dundee, Jacob M / Dyer, Michael A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Previous studies have demonstrated the dynamic changes in chromatin structure during retinal development that correlate with changes in gene expression. However, a major limitation of those prior studies was the lack of cellular resolution. Here, we ... ...

    Abstract Previous studies have demonstrated the dynamic changes in chromatin structure during retinal development that correlate with changes in gene expression. However, a major limitation of those prior studies was the lack of cellular resolution. Here, we integrate single-cell (sc) RNA-seq and scATAC-seq with bulk retinal data sets to identify cell type-specific changes in the chromatin structure during development. Although most genes' promoter activity is strongly correlated with chromatin accessibility, we discovered several hundred genes that were transcriptionally silent but had accessible chromatin at their promoters. Most of those silent/accessible gene promoters were in the Müller glial cells. The Müller cells are radial glia of the retina and perform a variety of essential functions to maintain retinal homeostasis and respond to stress, injury, or disease. The silent/accessible genes in Müller glia are enriched in pathways related to inflammation, angiogenesis, and other types of cell-cell signaling and were rapidly activated when we tested 15 different physiologically relevant conditions to mimic retinal stress, injury, or disease in human and murine retinae. We refer to these as "pliancy genes" because they allow the Müller glia to rapidly change their gene expression and cellular state in response to different types of retinal insults. The Müller glial cell pliancy program is established during development, and we demonstrate that pliancy genes are necessary and sufficient for regulating inflammation in the murine retina in vivo. In zebrafish, Müller glia can de-differentiate and form retinal progenitor cells that replace lost neurons. The pro-inflammatory pliancy gene cascade is not activated in zebrafish Müller glia following injury, and we propose a model in which species-specific pliancy programs underly the differential response to retinal damage in species that can regenerate retinal neurons (zebrafish) versus those that cannot (humans and mice).
    Language English
    Publishing date 2023-10-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.15.562396
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Identification of a modular super-enhancer in murine retinal development.

    Honnell, Victoria / Norrie, Jackie L / Patel, Anand G / Ramirez, Cody / Zhang, Jiakun / Lai, Yu-Hsuan / Wan, Shibiao / Dyer, Michael A

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 253

    Abstract: Super-enhancers are expansive regions of genomic DNA comprised of multiple putative enhancers that contribute to the dynamic gene expression patterns during development. This is particularly important in neurogenesis because many essential transcription ... ...

    Abstract Super-enhancers are expansive regions of genomic DNA comprised of multiple putative enhancers that contribute to the dynamic gene expression patterns during development. This is particularly important in neurogenesis because many essential transcription factors have complex developmental stage- and cell-type specific expression patterns across the central nervous system. In the developing retina, Vsx2 is expressed in retinal progenitor cells and is maintained in differentiated bipolar neurons and Müller glia. A single super-enhancer controls this complex and dynamic pattern of expression. Here we show that deletion of one region disrupts retinal progenitor cell proliferation but does not affect cell fate specification. The deletion of another region has no effect on retinal progenitor cell proliferation but instead leads to a complete loss of bipolar neurons. This prototypical super-enhancer may serve as a model for dissecting the complex gene expression patterns for neurogenic transcription factors during development. Moreover, it provides a unique opportunity to alter expression of individual transcription factors in particular cell types at specific stages of development. This provides a deeper understanding of function that cannot be achieved with traditional knockout mouse approaches.
    MeSH term(s) Animals ; CRISPR-Cas Systems ; Cell Differentiation/genetics ; Cell Proliferation ; Epigenomics ; Female ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/chemistry ; Homeodomain Proteins/genetics ; Male ; Mice ; Neurogenesis/genetics ; Neurogenesis/physiology ; Neuroglia/physiology ; Neurons/metabolism ; Regulatory Sequences, Nucleic Acid/genetics ; Retina/metabolism ; Stem Cells/physiology ; Transcription Factors/chemistry ; Transcription Factors/physiology
    Chemical Substances Homeodomain Proteins ; Transcription Factors ; Vsx2 protein, mouse
    Language English
    Publishing date 2022-01-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-27924-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Retinoblastoma from human stem cell-derived retinal organoids.

    Norrie, Jackie L / Nityanandam, Anjana / Lai, Karen / Chen, Xiang / Wilson, Matthew / Stewart, Elizabeth / Griffiths, Lyra / Jin, Hongjian / Wu, Gang / Orr, Brent / Tran, Quynh / Allen, Sariah / Reilly, Colleen / Zhou, Xin / Zhang, Jiakun / Newman, Kyle / Johnson, Dianna / Brennan, Rachel / Dyer, Michael A

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 4535

    Abstract: Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. Children with germline mutations in RB1 have a high likelihood of developing retinoblastoma and other malignancies later in life. ... ...

    Abstract Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. Children with germline mutations in RB1 have a high likelihood of developing retinoblastoma and other malignancies later in life. Genetically engineered mouse models of retinoblastoma share some similarities with human retinoblastoma but there are differences in their cellular differentiation. To develop a laboratory model of human retinoblastoma formation, we make induced pluripotent stem cells (iPSCs) from 15 participants with germline RB1 mutations. Each of the stem cell lines is validated, characterized and then differentiated into retina using a 3-dimensional organoid culture system. After 45 days in culture, the retinal organoids are dissociated and injected into the vitreous of eyes of immunocompromised mice to support retinoblastoma tumor growth. Retinoblastomas formed from retinal organoids made from patient-derived iPSCs have molecular, cellular and genomic features indistinguishable from human retinoblastomas. This model of human cancer based on patient-derived iPSCs with germline cancer predisposing mutations provides valuable insights into the cellular origins of this debilitating childhood disease as well as the mechanism of tumorigenesis following RB1 gene inactivation.
    MeSH term(s) Adult ; Cell Differentiation ; Cell Line ; Epigenesis, Genetic ; Exons/genetics ; Female ; Genome, Human ; Germ-Line Mutation/genetics ; Humans ; Imaging, Three-Dimensional ; Induced Pluripotent Stem Cells/metabolism ; Organoids/pathology ; Retina/pathology ; Retinoblastoma/genetics ; Retinoblastoma/pathology ; Retinoblastoma Protein/genetics ; Stem Cells/pathology
    Chemical Substances Retinoblastoma Protein
    Language English
    Publishing date 2021-07-27
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-24781-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma.

    Patel, Anand G / Chen, Xiang / Huang, Xin / Clay, Michael R / Komorova, Natalia / Krasin, Matthew J / Pappo, Alberto / Tillman, Heather / Orr, Brent A / McEvoy, Justina / Gordon, Brittney / Blankenship, Kaley / Reilly, Colleen / Zhou, Xin / Norrie, Jackie L / Karlstrom, Asa / Yu, Jiyang / Wodarz, Dominik / Stewart, Elizabeth /
    Dyer, Michael A

    Developmental cell

    2022  Volume 57, Issue 10, Page(s) 1226–1240.e8

    Abstract: Rhabdomyosarcoma (RMS) is a pediatric cancer with features of skeletal muscle; patients with unresectable or metastatic RMS fare poorly due to high rates of disease recurrence. Here, we use single-cell and single-nucleus RNA sequencing to show that RMS ... ...

    Abstract Rhabdomyosarcoma (RMS) is a pediatric cancer with features of skeletal muscle; patients with unresectable or metastatic RMS fare poorly due to high rates of disease recurrence. Here, we use single-cell and single-nucleus RNA sequencing to show that RMS tumors recapitulate the spectrum of embryonal myogenesis. Using matched patient samples from a clinical trial and orthotopic patient-derived xenografts (O-PDXs), we show that chemotherapy eliminates the most proliferative component with features of myoblasts within embryonal RMS; after treatment, the immature population with features of paraxial mesoderm expands to reconstitute the developmental hierarchy of the original tumor. We discovered that this paraxial mesoderm population is dependent on EGFR signaling and is sensitive to EGFR inhibitors. Taken together, these data serve as a proof of concept that targeting each developmental state in embryonal RMS is an effective strategy for improving outcomes by preventing disease recurrence.
    MeSH term(s) Child ; Drug Resistance ; ErbB Receptors ; Humans ; Muscle Development/genetics ; Neoplasm Recurrence, Local ; Rhabdomyosarcoma/drug therapy ; Rhabdomyosarcoma/genetics ; Rhabdomyosarcoma/pathology ; Rhabdomyosarcoma, Embryonal/drug therapy ; Rhabdomyosarcoma, Embryonal/genetics ; Rhabdomyosarcoma, Embryonal/pathology
    Chemical Substances ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2022-04-27
    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.2022.04.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    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

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Nucleome Dynamics during Retinal Development.

    Norrie, Jackie L / Lupo, Marybeth S / Xu, Beisi / Al Diri, Issam / Valentine, Marc / Putnam, Daniel / Griffiths, Lyra / Zhang, Jiakun / Johnson, Dianna / Easton, John / Shao, Ying / Honnell, Victoria / Frase, Sharon / Miller, Shondra / Stewart, Valerie / Zhou, Xin / Chen, Xiang / Dyer, Michael A

    Neuron

    2019  Volume 104, Issue 3, Page(s) 512–528.e11

    Abstract: More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage- ... ...

    Abstract More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage-specific activity. We studied dynamic changes in the 3D chromatin landscape important for precisely orchestrated changes in gene expression during retinal development by ultra-deep in situ Hi-C analysis on murine retinae. We identified developmental-stage-specific changes in chromatin compartments and enhancer-promoter interactions. We developed a machine learning-based algorithm to map euchromatin and heterochromatin domains genome-wide and overlaid it with chromatin compartments identified by Hi-C. Single-cell ATAC-seq and RNA-seq were integrated with our Hi-C and previous ChIP-seq data to identify cell- and developmental-stage-specific super-enhancers (SEs). We identified a bipolar neuron-specific core regulatory circuit SE upstream of Vsx2, whose deletion in mice led to the loss of bipolar neurons.
    MeSH term(s) Animals ; Chromatin/metabolism ; Chromatin Immunoprecipitation Sequencing ; Enhancer Elements, Genetic ; Euchromatin/metabolism ; Gene Expression Regulation, Developmental/physiology ; Gene Regulatory Networks ; Heterochromatin/metabolism ; Homeodomain Proteins/genetics ; Machine Learning ; Mice ; Nuclear Lamina/metabolism ; Promoter Regions, Genetic ; RNA-Seq ; Receptors, Cytoplasmic and Nuclear/genetics ; Retina/cytology ; Retina/embryology ; Retina/metabolism ; Retina/ultrastructure ; Retinal Bipolar Cells/cytology ; Retinal Bipolar Cells/metabolism ; Retinal Rod Photoreceptor Cells/cytology ; Retinal Rod Photoreceptor Cells/metabolism ; Single-Cell Analysis ; Transcription Factors/genetics ; Lamin B Receptor
    Chemical Substances Chromatin ; Euchromatin ; Heterochromatin ; Homeodomain Proteins ; Receptors, Cytoplasmic and Nuclear ; Transcription Factors ; Vsx2 protein, mouse
    Language English
    Publishing date 2019-09-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2019.08.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2496: 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 92: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: MYCN amplification and ATRX mutations are incompatible in neuroblastoma.

    Zeineldin, Maged / Federico, Sara / Chen, Xiang / Fan, Yiping / Xu, Beisi / Stewart, Elizabeth / Zhou, Xin / Jeon, Jongrye / Griffiths, Lyra / Nguyen, Rosa / Norrie, Jackie / Easton, John / Mulder, Heather / Yergeau, Donald / Liu, Yanling / Wu, Jianrong / Van Ryn, Collin / Naranjo, Arlene / Hogarty, Michael D /
    Kamiński, Marcin M / Valentine, Marc / Pruett-Miller, Shondra M / Pappo, Alberto / Zhang, Jinghui / Clay, Michael R / Bahrami, Armita / Vogel, Peter / Lee, Seungjae / Shelat, Anang / Sarthy, Jay F / Meers, Michael P / George, Rani E / Mardis, Elaine R / Wilson, Richard K / Henikoff, Steven / Downing, James R / Dyer, Michael A

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 913

    Abstract: Aggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating mutations in tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene and inactivation of the ATRX tumor-suppressor gene correlate ... ...

    Abstract Aggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating mutations in tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene and inactivation of the ATRX tumor-suppressor gene correlate with high-risk disease and poor prognosis. Here we show that ATRX mutations and MYCN amplification are mutually exclusive across all ages and stages in neuroblastoma. Using human cell lines and mouse models, we found that elevated MYCN expression and ATRX mutations are incompatible. Elevated MYCN levels promote metabolic reprogramming, mitochondrial dysfunction, reactive-oxygen species generation, and DNA-replicative stress. The combination of replicative stress caused by defects in the ATRX-histone chaperone complex, and that induced by MYCN-mediated metabolic reprogramming, leads to synthetic lethality. Therefore, ATRX and MYCN represent an unusual example, where inactivation of a tumor-suppressor gene and activation of an oncogene are incompatible. This synthetic lethality may eventually be exploited to improve outcomes for patients with high-risk neuroblastoma.
    MeSH term(s) Animals ; Child, Preschool ; Cohort Studies ; Female ; Gene Amplification ; Humans ; Infant ; Male ; Mice ; Mitochondria/genetics ; Mitochondria/metabolism ; Mutation ; N-Myc Proto-Oncogene Protein/genetics ; N-Myc Proto-Oncogene Protein/metabolism ; Neuroblastoma/genetics ; Neuroblastoma/metabolism ; Reactive Oxygen Species/metabolism ; X-linked Nuclear Protein/genetics ; X-linked Nuclear Protein/metabolism
    Chemical Substances N-Myc Proto-Oncogene Protein ; Reactive Oxygen Species ; X-linked Nuclear Protein (EC 3.6.4.12)
    Language English
    Publishing date 2020-02-14
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-14682-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top