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Nano-Vesicle (Mis)Communication In Senescence-Related Pathologies, Sherin Saheera, Ajay Godwin Potnuri, Prasanna Krishnamurthy 2020 University of Massachusetts Medical School

Nano-Vesicle (Mis)Communication In Senescence-Related Pathologies, Sherin Saheera, Ajay Godwin Potnuri, Prasanna Krishnamurthy

COVID-19 Publications by UMMS Authors

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role ...


Pfred: A Computational Platform For Sirna And Antisense Oligonucleotides Design, Simone Sciabola, Hualin Xi, Dario Cruz, Qing Cao, Christine Lawrence, Tianhong Zhang, Sergio Rotstein, Jason D. Hughes, Daniel R. Caffrey, Robert Stanton 2020 Biogen

Pfred: A Computational Platform For Sirna And Antisense Oligonucleotides Design, Simone Sciabola, Hualin Xi, Dario Cruz, Qing Cao, Christine Lawrence, Tianhong Zhang, Sergio Rotstein, Jason D. Hughes, Daniel R. Caffrey, Robert Stanton

University of Massachusetts Medical School Faculty Publications

PFRED a software application for the design, analysis, and visualization of antisense oligonucleotides and siRNA is described. The software provides an intuitive user-interface for scientists to design a library of siRNA or antisense oligonucleotides that target a specific gene of interest. Moreover, the tool facilitates the incorporation of various design criteria that have been shown to be important for stability and potency. PFRED has been made available as an open-source project so the code can be easily modified to address the future needs of the oligonucleotide research community. A compiled version is available for downloading at https://github.com/pfred ...


The Rna Phosphatase Pir-1 Regulates Endogenous Small Rna Pathways In C. Elegans, Daniel A. Chaves, Hui Dai, Lichao Li, James J. Moresco, Myung Eun Oh, Darryl Conte Jr., John R. Yates III, Craig C. Mello, Weifeng Gu 2020 University of Massachusetts Medical School

The Rna Phosphatase Pir-1 Regulates Endogenous Small Rna Pathways In C. Elegans, Daniel A. Chaves, Hui Dai, Lichao Li, James J. Moresco, Myung Eun Oh, Darryl Conte Jr., John R. Yates Iii, Craig C. Mello, Weifeng Gu

University of Massachusetts Medical School Faculty Publications

Eukaryotic cells regulate 5' triphosphorylated (ppp-) RNAs to promote cellular functions and prevent recognition by antiviral RNA sensors. For example, RNA capping enzymes possess triphosphatase domains that remove the γ phosphates of ppp-RNAs during RNA capping. Members of the closely related PIR1 family of RNA polyphosphatases remove both the β and γ phosphates from ppp-RNAs. Here we show that C. elegans PIR-1 dephosphorylates ppp-RNAs made by cellular RdRPs and is required for the maturation of 26G-RNAs, Dicer-dependent small RNAs that regulate thousands of genes during spermatogenesis and embryogenesis. PIR-1 also regulates the CSR-1 22G-RNA pathway and has critical functions in ...


Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi 2020 University of Alberta

Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi

Pharmacy Faculty Articles and Research

COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against ...


Sars-Cov-2 Spike Protein Variant D614g Increases Infectivity And Retains Sensitivity To Antibodies That Target The Receptor Binding Domain., Leonid Yurkovetskiy, Thomas Nyalile, Yetao Wang, William E. Diehl, Ann Dauphin, Claudia Carbone, Kristen Veinotte, Shawn B. Egri, Pardis C. Sabeti, Christos Kyratsous, James B. Munro, Kuang Shen, Jeremy Luban 2020 University of Massachusetts Medical School

Sars-Cov-2 Spike Protein Variant D614g Increases Infectivity And Retains Sensitivity To Antibodies That Target The Receptor Binding Domain., Leonid Yurkovetskiy, Thomas Nyalile, Yetao Wang, William E. Diehl, Ann Dauphin, Claudia Carbone, Kristen Veinotte, Shawn B. Egri, Pardis C. Sabeti, Christos Kyratsous, James B. Munro, Kuang Shen, Jeremy Luban

COVID-19 Publications by UMMS Authors

Virus genome sequence variants that appear over the course of an outbreak can be exploited to map the trajectory of the virus from one susceptible host to another. While such variants are usually of no functional significance, in some cases they may allow the virus to transmit faster, change disease severity, or confer resistance to antiviral therapies. Since the discovery of SARS-CoV-2 as the cause of COVID-19, the virus has spread around the globe, and thousands of SARS-CoV-2 genomes have been sequenced. The rate of sequence variation among SARS-CoV-2 isolates is modest for an RNA virus but the enormous number ...


Crispr Deletion Of The C9orf72 Promoter In Als/Ftd Patient Motor Neurons Abolishes Production Of Dipeptide Repeat Proteins And Rescues Neurodegeneration, Gopinath Krishnan, Yu Zhang, Yuanzheng Gu, Mark W. Kankel, Fen-Biao Gao, Sandra Almeida 2020 University of Massachusetts Medical School

Crispr Deletion Of The C9orf72 Promoter In Als/Ftd Patient Motor Neurons Abolishes Production Of Dipeptide Repeat Proteins And Rescues Neurodegeneration, Gopinath Krishnan, Yu Zhang, Yuanzheng Gu, Mark W. Kankel, Fen-Biao Gao, Sandra Almeida

Open Access Articles

GGGGCC (G4C2) repeat expansion in the first intron of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Brain tissues from affected individuals show characteristic nuclear RNA foci containing the expanded repeat RNAs, as well as neuronal inclusions containing dipeptide repeat (DPR) proteins [poly(GA), poly(GP), poly(GR), poly(PR), and poly(PA)] resulting from the translation of both sense and antisense repeat RNAs in all reading frames. Although reduced C9ORF72 protein function may contribute to disease, the more likely drivers of disease are mechanisms related to a gain of toxic function ...


Ribosome Engineering Reveals The Importance Of 5s Rrna Autonomy For Ribosome Assembly, Shijie Huang, Nikolay A. Aleksashin, Anna B. Loveland, Dorota Klepacki, Kaspar Reier, Amira Kefi, Teresa Szal, Jaanus Remme, Luc Jaeger, Nora Vazquez-Laslop, Andrei A. Korostelev, Alexander S. Mankin 2020 The University of Illinois at Chicago

Ribosome Engineering Reveals The Importance Of 5s Rrna Autonomy For Ribosome Assembly, Shijie Huang, Nikolay A. Aleksashin, Anna B. Loveland, Dorota Klepacki, Kaspar Reier, Amira Kefi, Teresa Szal, Jaanus Remme, Luc Jaeger, Nora Vazquez-Laslop, Andrei A. Korostelev, Alexander S. Mankin

Open Access Articles

5S rRNA is an indispensable component of cytoplasmic ribosomes in all species. The functions of 5S rRNA and the reasons for its evolutionary preservation as an independent molecule remain unclear. Here we used ribosome engineering to investigate whether 5S rRNA autonomy is critical for ribosome function and cell survival. By linking circularly permutated 5S rRNA with 23S rRNA we generated a bacterial strain devoid of free 5S rRNA. Viability of the engineered cells demonstrates that autonomous 5S rRNA is dispensable for cell growth under standard conditions and is unlikely to have essential functions outside the ribosome. The fully assembled ribosomes ...


Synthesis, Characterisation And Biological Evaluation Of Tyramine Derived Schiff Base Ligand And Its Transition Metal(Ii) Complexes, Abdul Khader Jailani, N.S.K. Gowthaman, Mookkandi Palsamy Kesavan 2020 Hajee Karutha Rowther Howdia College, Uthamapalayam-625 533,Tamil Nadu,India.

Synthesis, Characterisation And Biological Evaluation Of Tyramine Derived Schiff Base Ligand And Its Transition Metal(Ii) Complexes, Abdul Khader Jailani, N.S.K. Gowthaman, Mookkandi Palsamy Kesavan

Karbala International Journal of Modern Science

In this study, a new tyramine derived Schiff base ligand (L) (L=1,3-phenylene-bis-4-aminoantipyrinyl-4-aminoethylphenol) and its derived transition metal(II) complexes [Cu(L)Cl2](1), [Ni(L)Cl2](2), [Co(L)Cl2] (3) and [Zn(L)Cl2] (4) have been synthesized and well characterized by the way of different spectroscopic and analytical techniques. Analytical and spectroscopic studies result suggests that metal(II) complexes more probably have octahedral geometry. DNA binding tendency of L and metal(II) complexes 1-4 have been assessed by probing their ability to bind with Calf Thymus DNA (CT-DNA) via electronic absorption and ...


Core Binding Factor Leukemia Hijacks T-Cell Prone Pu.1 Antisense Promoter, E. van der Kouwe, Lucio H. Castilla, D. G. Tenen, P. B. Staber 2020 Medical University of Vienna

Core Binding Factor Leukemia Hijacks T-Cell Prone Pu.1 Antisense Promoter, E. Van Der Kouwe, Lucio H. Castilla, D. G. Tenen, P. B. Staber

University of Massachusetts Medical School Faculty Publications

The blood system serves as a key model for cell differentiation and cancer. It is orchestrated by precise spatiotemporal expression of the hematopoietic master regulator PU.114. PU.1 gene expression is regulated through enhancer-promoter interactions within a topologically associated domain (TAD)5,6. PU.1 levels increase during myeloid differentiation while failure to do so results in myeloid leukemia7. In contrast, T-cell differentiation requires PU.1 to be completely switched off810. Little is known about the precise mechanisms of PU.1 repression, physiological as in T-cell differentiation, or pathological as in leukemia. Here we ...


Association Of Dtnbp1 With Schizophrenia: Findings From Two Independent Samples Of Han Chinese Population, Yongfeng Yang, Xiaoduo Fan, Ge Yang 2020 Xinxiang Medical University

Association Of Dtnbp1 With Schizophrenia: Findings From Two Independent Samples Of Han Chinese Population, Yongfeng Yang, Xiaoduo Fan, Ge Yang

Psychiatry Publications

Objectives: Schizophrenia (SZ) is a complex psychiatric disorder that has a strong genetic basis. Dystrobrevin-binding protein 1 (DTNBP1) is one of the genes thought to be pivotal in regulating the glutamatergic system. Studies have suggested that variations in DTNBP1 confer susceptibility to SZ and clinical symptoms. Here, we performed a two-stage independent verification study to identify polymorphisms of the DTNBP1 gene that might be associated with SZ in the Han Chinese population.

Methods: In stage 1, 14 single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 healthy controls (HCs) using the Illumina GoldenGate assays on a ...


Mrna Stem-Loops Can Pause The Ribosome By Hindering A-Site Trna Binding, Chen Bao, Sarah Loerch, Clarence Ling, Andrei A. Korostelev, Nikolaus Grigorieff, Dmitri N. Ermolenko 2020 University of Rochester

Mrna Stem-Loops Can Pause The Ribosome By Hindering A-Site Trna Binding, Chen Bao, Sarah Loerch, Clarence Ling, Andrei A. Korostelev, Nikolaus Grigorieff, Dmitri N. Ermolenko

Open Access Articles

Although the elongating ribosome is an efficient helicase, certain mRNA stem-loop structures are known to impede ribosome movement along mRNA and stimulate programmed ribosome frameshifting via mechanisms that are not well understood. Using biochemical and single-molecule Forster resonance energy transfer (smFRET) experiments, we studied how frameshift-inducing stem-loops from E. coli dnaX mRNA and the gag-pol transcript of Human Immunodeficiency Virus (HIV) perturb translation elongation. We find that upon encountering the ribosome, the stem-loops strongly inhibit A-site tRNA binding and ribosome intersubunit rotation that accompanies translation elongation. Electron cryo-microscopy (cryo-EM) reveals that the HIV stem-loop docks into the A site of ...


A Cas9 With Pam Recognition For Adenine Dinucleotides, Pranam Chatterjee, Jooyoung Lee, Lisa Nip, Sabrina R. T. Koseki, Emma Tysinger, Erik J. Sontheimer, Joseph M. Jacobson, Noah Jakimo 2020 Massachusetts Institute of Technology

A Cas9 With Pam Recognition For Adenine Dinucleotides, Pranam Chatterjee, Jooyoung Lee, Lisa Nip, Sabrina R. T. Koseki, Emma Tysinger, Erik J. Sontheimer, Joseph M. Jacobson, Noah Jakimo

Open Access Articles

CRISPR-associated (Cas) DNA-endonucleases are remarkably effective tools for genome engineering, but have limited target ranges due to their protospacer adjacent motif (PAM) requirements. We demonstrate a critical expansion of the targetable sequence space for a type II-A CRISPR-associated enzyme through identification of the natural 5[Formula: see text]-NAAN-3[Formula: see text] PAM preference of Streptococcus macacae Cas9 (SmacCas9). To achieve efficient editing activity, we graft the PAM-interacting domain of SmacCas9 to its well-established ortholog from Streptococcus pyogenes (SpyCas9), and further engineer an increased efficiency variant (iSpyMac) for robust genome editing activity. We establish that our hybrids can target all ...


Comparative Antiviral Activity Of Remdesivir And Anti-Hiv Nucleoside Analogs Against Human Coronavirus 229e (Hcov-229e), Keykavous Parang, Naglaa Salem El-Sayed, Assad J. Kazeminy, Rakesh Tiwari 2020 Chapman University

Comparative Antiviral Activity Of Remdesivir And Anti-Hiv Nucleoside Analogs Against Human Coronavirus 229e (Hcov-229e), Keykavous Parang, Naglaa Salem El-Sayed, Assad J. Kazeminy, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act ...


Yap1/Taz Drives Ependymoma-Like Tumour Formation In Mice, Noreen Eder, Federico Roncaroli, Marie-Charlotte Dolmart, Stuart Horswell, Felipe Andreiuolo, Helen R. Flynn, Andre T. Lopes, Suzanne Claxton, John-Paul Kilday, Lucy Collinson, Junhao Mao, Torsten Pietsch, Barry Thompson, Ambrosius P. Snijders, Sila K. Ultanir 2020 The Francis Crick Institute

Yap1/Taz Drives Ependymoma-Like Tumour Formation In Mice, Noreen Eder, Federico Roncaroli, Marie-Charlotte Dolmart, Stuart Horswell, Felipe Andreiuolo, Helen R. Flynn, Andre T. Lopes, Suzanne Claxton, John-Paul Kilday, Lucy Collinson, Junhao Mao, Torsten Pietsch, Barry Thompson, Ambrosius P. Snijders, Sila K. Ultanir

Open Access Articles

YAP1 gene fusions have been observed in a subset of paediatric ependymomas. Here we show that, ectopic expression of active nuclear YAP1 (nlsYAP5SA) in ventricular zone neural progenitor cells using conditionally-induced NEX/NeuroD6-Cre is sufficient to drive brain tumour formation in mice. Neuronal differentiation is inhibited in the hippocampus. Deletion of YAP1's negative regulators LATS1 and LATS2 kinases in NEX-Cre lineage in double conditional knockout mice also generates similar tumours, which are rescued by deletion of YAP1 and its paralog TAZ. YAP1/TAZ-induced mouse tumours display molecular and ultrastructural characteristics of human ependymoma. RNA sequencing and quantitative proteomics of ...


Tim, A Targeted Insertional Mutagenesis Method Utilizing Crispr/Cas9 In Chlamydomonas Reinhardtii, Tyler Picariello, Yuqing Hou, Tomohiro Kubo, Nathan A. McNeill, Haru-Aki Yanagisawa, Toshiyuki Oda, George B. Witman 2020 University of Massachusetts Medical School

Tim, A Targeted Insertional Mutagenesis Method Utilizing Crispr/Cas9 In Chlamydomonas Reinhardtii, Tyler Picariello, Yuqing Hou, Tomohiro Kubo, Nathan A. Mcneill, Haru-Aki Yanagisawa, Toshiyuki Oda, George B. Witman

Radiology Publications

Generation and subsequent analysis of mutants is critical to understanding the functions of genes and proteins. Here we describe TIM, an efficient, cost-effective, CRISPR-based targeted insertional mutagenesis method for the model organism Chlamydomonas reinhardtii. TIM utilizes delivery into the cell of a Cas9-guide RNA (gRNA) ribonucleoprotein (RNP) together with exogenous double-stranded (donor) DNA. The donor DNA contains gene-specific homology arms and an integral antibiotic-resistance gene that inserts at the double-stranded break generated by Cas9. After optimizing multiple parameters of this method, we were able to generate mutants for six out of six different genes in two different cell-walled strains with ...


The Snakeskin-Mesh Complex Of Smooth Septate Junction Restricts Yorkie To Regulate Intestinal Homeostasis In Drosophila, Hsi-Ju Chen, Qi Li, Niraj K. Nirala, Y. Tony Ip 2020 University of Massachusetts Medical School

The Snakeskin-Mesh Complex Of Smooth Septate Junction Restricts Yorkie To Regulate Intestinal Homeostasis In Drosophila, Hsi-Ju Chen, Qi Li, Niraj K. Nirala, Y. Tony Ip

Open Access Articles

Tight junctions in mammals and septate junctions in insects are essential for epithelial integrity. We show here that, in the Drosophila intestine, smooth septate junction proteins provide barrier and signaling functions. During an RNAi screen for genes that regulate adult midgut tissue growth, we found that loss of two smooth septate junction components, Snakeskin and Mesh, caused a hyperproliferation phenotype. By examining epitope-tagged endogenous Snakeskin and Mesh, we demonstrate that the two proteins are present in the cytoplasm of differentiating enteroblasts and in cytoplasm and septate junctions of mature enterocytes. In both enteroblasts and enterocytes, loss of Snakeskin and Mesh ...


Fmrp Links Optimal Codons To Mrna Stability In Neurons, Huan Shu, Elisa Donnard, Botao Liu, Ruijia Wang, Joel D. Richter 2020 University of Massachusetts Medical School

Fmrp Links Optimal Codons To Mrna Stability In Neurons, Huan Shu, Elisa Donnard, Botao Liu, Ruijia Wang, Joel D. Richter

University of Massachusetts Medical School Faculty Publications

Fragile X syndrome (FXS) is caused by inactivation of the FMR1 gene and loss of encoded FMRP, an RNA binding protein that represses translation of some of its target transcripts. Here we use ribosome profiling and RNA-seq to investigate the dysregulation of translation in the mouse brain cortex. We find that most changes in ribosome occupancy on hundreds of mRNAs are largely driven by dysregulation in transcript abundance. Many downregulated mRNAs, which are mostly responsible for neuronal and synaptic functions, are highly enriched for FMRP binding targets. RNA metabolic labeling demonstrates that in FMRP-deficient cortical neurons, mRNA downregulation is caused ...


Neuroligin3 Splice Isoforms Shape Inhibitory Synaptic Function In The Mouse Hippocampus, Motokazu Uchigashima, Ming Leung, Takuya Watanabe, Amy Cheung, Timmy Le, Sabine Pallat, Alexandre Luis Marques Dinis, Masahiko Watanabe, Yuka Imamura Kawasawa, Kensuke Futai 2020 University of Massachusetts Medical School

Neuroligin3 Splice Isoforms Shape Inhibitory Synaptic Function In The Mouse Hippocampus, Motokazu Uchigashima, Ming Leung, Takuya Watanabe, Amy Cheung, Timmy Le, Sabine Pallat, Alexandre Luis Marques Dinis, Masahiko Watanabe, Yuka Imamura Kawasawa, Kensuke Futai

Open Access Articles

Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, transsynaptic protein-protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate Neuroligin (Nlgn) genes that ...


Single Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis, Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech 2020 University of Massachusetts Medical School

Single Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis, Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

The “browning” of inguinal white adipose tissue (iWAT) through increased abundance of thermogenic beige/brite adipocytes is induced by cold exposure and many other perturbations in association with beneficial systemic metabolic effects. Adipose browning is reported to require activation of sympathetic nerve fibers (SNF), aided by alternately activated macrophages within iWAT. Here we demonstrate the first example of a non-cell autonomous pathway for iWAT browning that is fully independent of SNF activity. Thus, the strong induction of thermogenic adipocytes prompted by deletion of adipocyte fatty acid synthase (iAdFASNKO mice) was unaffected by denervation or the deletion of SNF modulator Neuregulin-4 ...


Sars-Cov-2 Receptor Ace2 Is An Interferon-Stimulated Gene In Human Airway Epithelial Cells And Is Detected In Specific Cell Subsets Across Tissues, Carly G. K. Ziegler, Yuming Cao, Zhiru Guo, Jennifer P. Wang, Robert W. Finberg, Manuel Garber, Alex K. Shalek, Jose Ordovas-Montanes, HCA Lung Biological Network 2020 Harvard Medical School

Sars-Cov-2 Receptor Ace2 Is An Interferon-Stimulated Gene In Human Airway Epithelial Cells And Is Detected In Specific Cell Subsets Across Tissues, Carly G. K. Ziegler, Yuming Cao, Zhiru Guo, Jennifer P. Wang, Robert W. Finberg, Manuel Garber, Alex K. Shalek, Jose Ordovas-Montanes, Hca Lung Biological Network

COVID-19 Publications by UMMS Authors

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung ...


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