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Full-Text Articles in Cells

Notch Signaling Represses Cone Photoreceptor Formation Through The Regulation Of Retinal Progenitor Cell States, Xueqing Chen, Mark M. Emerson Jul 2021

Notch Signaling Represses Cone Photoreceptor Formation Through The Regulation Of Retinal Progenitor Cell States, Xueqing Chen, Mark M. Emerson

Publications and Research

Notch signaling is required to repress the formation of vertebrate cone photoreceptors and to maintain the proliferative potential of multipotent retinal progenitor cells. However, the mechanism by which Notch signaling controls these processes is unknown. Recently, restricted retinal progenitor cells with limited proliferation capacity and that preferentially generate cone photoreceptors have been identified. Thus, there are several potential steps during cone genesis that Notch signaling could act. Here we use cell type specific cis-regulatory elements to localize the primary role of Notch signaling in cone genesis to the formation of restricted retinal progenitor cells from multipotent retinal progenitor cells. Localized …


Extracellular Vesicles Released By Human Retinal Pigment Epithelium Mediate Increased Polarised Secretion Of Drusen Proteins In Response To Amd Stressors, Miguel Flores-Bellver, Jason Mighty, Silvia Aparicio-Domingo, Kang V. Li, Cui Shi, Jing Zhou, Hannah Cobb, Patrick Mcgrath, German Michelis, Patricia Lenhart, Ganna Bilousova, Søren Heissel, Michael J. Rudy, Christina Coughlan, Andrew E. Goodspeed, S. Patricia Becerra, Stephen Redenti, M. Valeria Canto-Soler Jan 2021

Extracellular Vesicles Released By Human Retinal Pigment Epithelium Mediate Increased Polarised Secretion Of Drusen Proteins In Response To Amd Stressors, Miguel Flores-Bellver, Jason Mighty, Silvia Aparicio-Domingo, Kang V. Li, Cui Shi, Jing Zhou, Hannah Cobb, Patrick Mcgrath, German Michelis, Patricia Lenhart, Ganna Bilousova, Søren Heissel, Michael J. Rudy, Christina Coughlan, Andrew E. Goodspeed, S. Patricia Becerra, Stephen Redenti, M. Valeria Canto-Soler

Publications and Research

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Drusen are key contributors to the etiology of AMD and the ability to modulate drusen biogenesis could lead to therapeutic strategies to slow or halt AMD progression. The mechanisms underlying drusen biogenesis, however, remain mostly unknown. Here we demonstrate that under homeostatic conditions extracellular vesicles (EVs) secreted by retinal pigment epithelium (RPE) cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology, including oxidative stress, immune response, inflammation, complement system and drusen composition. Furthermore, we provide first evidence that drusen-associated proteins are released as cargo of extracellular …


Human Retinal Organoids Release Extracellular Vesicles That Regulate Gene Expression In Target Human Retinal Progenitor Cells, Jing Zhou, Miguel Flores‑Bellver, Jianbo Pan, Alberto Benito‑Martin, Cui Shi, Onyekwere Onwumere, Jason Mighty, Jiang Qian, Xiufeng Zhong, Tasmim Hogue, Baffour Amponsah‑Antwi, Linda Einbond, Rajendra Gharbaran, Hao Wu, Bo‑Juen Chen, Zhiliang Zheng, Tatyana Tchaikovskaya, Xusheng Zhang, Hector Peinado, Maria Valeria Canto‑Soler, Stephen Redenti Jan 2021

Human Retinal Organoids Release Extracellular Vesicles That Regulate Gene Expression In Target Human Retinal Progenitor Cells, Jing Zhou, Miguel Flores‑Bellver, Jianbo Pan, Alberto Benito‑Martin, Cui Shi, Onyekwere Onwumere, Jason Mighty, Jiang Qian, Xiufeng Zhong, Tasmim Hogue, Baffour Amponsah‑Antwi, Linda Einbond, Rajendra Gharbaran, Hao Wu, Bo‑Juen Chen, Zhiliang Zheng, Tatyana Tchaikovskaya, Xusheng Zhang, Hector Peinado, Maria Valeria Canto‑Soler, Stephen Redenti

Publications and Research

The mechanisms underlying retinal development have not been completely elucidated. Extracellular vesicles (EVs) are novel essential mediators of cell‑to‑cell communication with emerging roles in developmental processes. Nevertheless, the identification of EVs in human retinal tissue, characterization of their cargo, and analysis of their potential role in retina development has not been accomplished. Three‑dimensional retinal tissue derived from human induced pluripotent stem cells (hiPSC) provide an ideal developmental system to achieve this goal. Here we report that hiPSC‑derived retinal organoids release exosomes and microvesicles with small noncoding RNA cargo. EV miRNA cargo‑predicted targetome correlates with Gene Ontology (GO) pathways involved in …


Integrating Ligand-Receptor Interactions And In Vitro Evolution For Streamlined Discovery Of Artificial Nucleic Acid Ligands, Hasan E. Zumrut, Sana Batool, Kimon V. Argyropoulos, Nicole Williams, Roksana Azad, Prabodhika R. Mallikaratchy Sep 2019

Integrating Ligand-Receptor Interactions And In Vitro Evolution For Streamlined Discovery Of Artificial Nucleic Acid Ligands, Hasan E. Zumrut, Sana Batool, Kimon V. Argyropoulos, Nicole Williams, Roksana Azad, Prabodhika R. Mallikaratchy

Publications and Research

To discover DNA ligands against a predetermined receptor protein complex, we introduce a comprehensive version of ligand-guided selection (LIGS). LIGS is, itself, a variant of systematic evolution of ligands by exponential enrichment (SELEX). Herein, we have optimized LIGS to identify higher affinity aptamers with high specificity. In addition, we demonstrate the expandability of LIGS by performing specific aptamer elution at 25C, utilizing multiple monoclonal antibodies (mAbs) against cultured cells and primary cells obtained from human donors expressing the same receptor. Eluted LIGS libraries obtained through Illumina high-throughput (HT) DNA sequencing were analyzed by bioinformatics tools to discover five DNA aptamers …


An Ensemble Of Flexible Conformations Underlies Mechanotransduction By The Cadherin–Catenin Adhesion Complex, Martin Bush, Bashir M. Alhanshali, Shuo Qian, Christopher B. Stanley, William T. Heller, Tsutomu Matsui, Thomas M. Weiss, Iain D. Nicholl, Thomas Walz, David J. E. Callaway, Zimei Bu Jan 2019

An Ensemble Of Flexible Conformations Underlies Mechanotransduction By The Cadherin–Catenin Adhesion Complex, Martin Bush, Bashir M. Alhanshali, Shuo Qian, Christopher B. Stanley, William T. Heller, Tsutomu Matsui, Thomas M. Weiss, Iain D. Nicholl, Thomas Walz, David J. E. Callaway, Zimei Bu

Publications and Research

The cadherin–catenin adhesion complex is the central component of the cell–cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the α-catenin•β-catenin•epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible “tongue” that is inserted into α-catenin and participates in the …


Centrosomal Kinase Nek2 Cooperates With Oncogenic Pathways To Promote Metastasis, T K. Das, Dibyendu Dana, Suneeta S. Paroly, S. K. Perumal, S. Singh, H. Jhun, J. Pendse, R. L. Cagan, T. T. Talele, Sanjai Kumar Sep 2013

Centrosomal Kinase Nek2 Cooperates With Oncogenic Pathways To Promote Metastasis, T K. Das, Dibyendu Dana, Suneeta S. Paroly, S. K. Perumal, S. Singh, H. Jhun, J. Pendse, R. L. Cagan, T. T. Talele, Sanjai Kumar

Publications and Research

Centrosomal kinase Nek2 is overexpressed in different cancers, yet how it contributes toward tumorigenesis remains poorly understood. dNek2 overexpression in a Drosophila melanogaster model led to upregulation of Drosophila Wnt ortholog wingless (Wg), and alteration of cell migration markers—Rho1, Rac1 and E-cadherin (Ecad)—resulting in changes in cell shape and tissue morphogenesis. dNek2 overexpression cooperated with receptor tyrosine kinase and mitogen-activated protein kinase signaling to upregulate activated Akt, Diap1, Mmp1 and Wg protein to promote local invasion, distant seeding and metastasis. In tumor cell injection assays, dNek2 cooperated with Ras and Src signaling to promote aggressive colonization of tumors into different …