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3 results on '"Margaret A. Clement"'

1. Depletion of METTL3 alters cellular and extracellular levels of miRNAs containing m6A consensus sequences

Author

Jessica J. Abner, Jeffrey L. Franklin, Margaret A. Clement, Scott A. Hinger, Ryan M. Allen, Xiao Liu, Stefanie Kellner, Junzhou Wu, John Karijolich, Qi Liu, Kasey C. Vickers, Peter Dedon, Alissa M. Weaver, Robert J. Coffey, and James G. Patton

Subjects
miRNA, Base modification, Extracellular vesicle, m6A, RNA, Tumor microenvironment, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Extracellular vesicles (EVs) are capable of transferring cargo from donor to recipient cells, but precisely how cargo content is regulated for export is mostly unknown. For miRNA cargo, we previously showed that when compared to isogenic colorectal cancer (CRC) cells expressing wild-type KRAS, a distinct subset of miRNAs are differentially enriched in EVs from KRAS mutant active CRC cells, with miR-100 being one of the most enriched. The mechanisms that could explain how miR-100 and other miRNAs are differentially exported into EVs have not been fully elucidated. Here, we tested the effect of N6-methyladenosine (m6A) modification on miRNA export into EVs by depletion of METTL3 and ALKBH5, a writer and eraser of m6A modification, respectively. While the effects of ALKBH5 knockdown were quite modest, decreased levels of METTL3 led to reduced cellular and extracellular levels of a subset of miRNAs that contain consensus sequences for m6A modification. Functional testing of EVs prepared from cells expressing shRNAs against METTL3 showed that they were less capable of conferring colony growth in 3D to wild-type KRAS cells and were also largely incapable of conferring the spread of cetuximab resistance. Our data support a role for METTL3 modification on cellular miRNA levels and export of specific miRNAs.

Published
2021
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2. Induction of a proliferative response in the zebrafish retina by injection of extracellular vesicles

Author

Sankarathi Balaiya, Qi Liu, Dominic Didiano, Scott Hinger, Edward M. Levine, Xiaozhuan Dai, James G. Patton, Matthew R Kent, Margaret A. Clement, Zachary Flickinger, and Jessica J. Abner

Subjects
Proteomics, Neurogenesis, Biology, Article, Retina, Injections, Animals, Genetically Modified, Cellular and Molecular Neuroscience, Extracellular Vesicles, medicine, Animals, Progenitor cell, Zebrafish, Cells, Cultured, Retinal regeneration, Cell Proliferation, Gene knockdown, Regeneration (biology), Extracellular vesicle, Zebrafish Proteins, biology.organism_classification, Sensory Systems, Cell biology, Ophthalmology, medicine.anatomical_structure, Photoreceptor Cells, Invertebrate, Muller glia
Abstract

Ongoing research using cell transplantation and viral-mediated gene therapy has been making progress to restore vision by retinal repair, but targeted delivery and complete cellular integration remain challenging. An alternative approach is to induce endogenous Muller glia (MG) to regenerate lost neurons and photoreceptors, as occurs spontaneously in teleost fish and amphibians. Extracellular vesicles (EVs) can transfer protein and RNA cargo between cells serving as a novel means of cell-cell communication. We conducted an in vivo screen in zebrafish to identify sources of EVs that could induce MG to dedifferentiate and generate proliferating progenitor cells after intravitreal injection into otherwise undamaged zebrafish eyes. Small EVs (sEVs) from C6 glioma cells were the most consistent at inducing MG-derived proliferating cells. Ascl1a expression increased after intravitreal injection of C6 sEVs and knockdown of ascl1a inhibited the induction of proliferation. Proteomic and RNAseq analyses of EV cargo content were performed to begin to identify key factors that might target EVs to MG and initiate retina regeneration.

Published
2020

3. Working women in an urban setting: traders, vendors, and food security in Accra

Author

Levin, Carol E.; Ruel, Marie T.; Morris, Saul Sutkover; Maxwell, Daniel G.; Armar-Klemesu, Margaret; Ahiadeke, Clement, http://orcid.org/0000-0002-9506-348X Ruel, Marie, Levin, Carol E.; Ruel, Marie T.; Morris, Saul Sutkover; Maxwell, Daniel G.; Armar-Klemesu, Margaret; Ahiadeke, Clement, and http://orcid.org/0000-0002-9506-348X Ruel, Marie

Abstract

PR, ISI; IFPRI3; MP-14; Theme 12, FCND

Published
1999

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