Stem Cells

Aging (Aging-US)

Aging-US published this trending research paper in Volume 14, Issue 24, entitled, "Transcriptomic analysis of human ALS skeletal muscle reveals a disease-specific pattern of dysregulated circRNAs" by researchers from Laboratory of Genetics and Genomics, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD; Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL; Birmingham Veterans Affairs Medical Center, Birmingham, AL; Center for Neural Science and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA; Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama at Birmingham, Birmingham, AL; Cell, Developmental, and Integrative Biology, The University of Alabama at Birmingham, Birmingham, AL.

DOI - https://doi.org/10.18632/aging.204450

Corresponding authors - Myriam Gorospe - GorospeM@grc.nia.nih.gov, Dimitrios Tsitsipatis - dimitrios.tsitsipatis@nih.gov, Peter H. King - phking@uabmc.edu 

Abstract

Circular RNAs are abundant, covalently closed transcripts that arise in cells through back-splicing and display distinct expression patterns across cells and developmental stages. While their functions are largely unknown, their intrinsic stability has made them valuable biomarkers in many diseases. Here, we set out to examine circRNA patterns in amyotrophic lateral sclerosis (ALS). By RNA-sequencing analysis, we first identified circRNAs and linear RNAs that were differentially abundant in skeletal muscle biopsies from ALS compared to normal individuals. By RT-qPCR analysis, we confirmed that 8 circRNAs were significantly elevated and 10 were significantly reduced in ALS, while the linear mRNA counterparts, arising from shared precursor RNAs, generally did not change. Several of these circRNAs were also differentially abundant in motor neurons derived from human induced pluripotent stem cells (iPSCs) bearing ALS mutations, and across different disease stages in skeletal muscle from a mouse model of ALS (SOD1G93A). Interestingly, a subset of the circRNAs significantly elevated in ALS muscle biopsies were significantly reduced in the spinal cord samples from ALS patients and ALS (SOD1G93A) mice. In sum, we have identified differentially abundant circRNAs in ALS-relevant tissues (muscle and spinal cord) that could inform about neuromuscular molecular programs in ALS and guide the development of therapies.

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Keywords - aging, amyotrophic lateral sclerosis, circular RNAs, neurodegenerative disease, human skeletal muscle, human spinal cord tissue

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

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Facebook - https://www.facebook.com/AgingUS/
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Transcriptomic Analysis of Human ALS Skeletal Muscle Reveals…

Teach Me in 10

Cell culture media is one of the most important components of the in vitro tissue environment. It provides the nutrients, minerals and growth factors necessary to sustain cells outside the body. 

This Teach Me in 10 explores the different media options available for plating mammalian cells. It covers preparation techniques, storage options, and how to choose the right media for your experiment.

Plating Cells: Preparation and Media Options With Ann Rossi Bilodeau

In advanced therapy medicinal products (ATMP) manufacturing, the quality and safety of the product need to be ensured from the first stages of development. 

In this episode, we are joined by Kris Wronski, Cell Culture Applications Scientist from Thermo Fisher Scientific. He will discuss how to design an effective contamination prevention strategy that will minimize risks to cell therapy products and allow you to implement appropriate control measures.

By watching this episode you will learn:
•	Why contamination prevention strategy is so important
•	About the types and sources of particulates in the cell therapy production environment and their impact on product quality and safety 
•	The role of laboratory equipment in contamination prevention and what to look for when sourcing suitable equipment

Contamination Prevention in Cell Therapy Environments With Kris Wronski

Oncotarget

Oncotarget published this trending research paper in Volume 13, entitled, "HDAC inhibitors suppress protein poly(ADP-ribosyl)ation and DNA repair protein levels and phosphorylation status in hematologic cancer cells: implications for their use in combination with PARP inhibitors and chemotherapeutic drugs" by researchers from the Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; Department of Experimental Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada.

DOI - https://doi.org/10.18632/oncotarget.28278

Correspondence to - Benigno C. Valdez - bvaldez@mdanderson.org 

Abstract

The therapeutic efficacy of histone deacetylase inhibitors (HDACi) for hematologic malignancies and solid tumors is attributed to their ability to remodel chromatin, normalize dysregulated gene expression, and inhibit repair of damaged DNA. Studies on the interactions of HDACi with PARP inhibitors in hematologic cancers are limited, especially when combined with chemotherapeutic agents. Exposure of hematologic cancer cell lines and patient-derived cell samples to various HDACi resulted in a significant caspase-independent inhibition of protein PARylation, mainly catalyzed by PARP1. HDACi affected the expression of PARP1 at the transcription and/or post-translation levels in a cell line-dependent manner. HDACi-mediated inhibition of PARylation correlated with decreased levels and phosphorylation of major proteins involved in DNA repair. Combination of HDAC and PARP1 inhibitors provided synergistic cytotoxicity, which was further enhanced when combined with a chemotherapeutic regimen containing gemcitabine, busulfan and melphalan as observed in lymphoma cell lines. Our results indicate that the anti-tumor efficacy of HDACi is partly due to down-regulation of PARylation, which negatively affects the status of DNA repair proteins. This repair inhibition, combined with the high levels of oxidative and DNA replication stress characteristic of cancer cells, could have conferred these hematologic cancer cells not only with a high sensitivity to HDACi but also with a heightened dependence on PARP and therefore with extreme sensitivity to combined HDACi/PARPi treatment and, by extension, to their combination with conventional DNA-damaging chemotherapeutic agents. The observed synergism of these drugs could have a major significance in improving treatment of these cancers.

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Keywords - poly(ADP-ribosyl)ation, HDAC inhibitors, PARP inhibitors, chemotherapy, hematologic malignancy

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

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Media Contact
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Paper Spotlight: Combination of HDACi, PARPi and Chemotherapeutic Agents Treat Hematologic Cancer

It's easy to see why organoids have become popular over the years. These 3D cell cultures can self-organize into "mini-organs" capable of recapitulating their respective organ-specific functions. Organoids have been developed for several types of human organs, including the brain, breast, colon, liver, pancreas, stomach, esophagus, small intestine, ovary, uterus, fallopian tubes, prostate and retina.

However, organoids are more complex compared to traditional 2D cultures and even 3D spheroids. Fortunately, products such as the Corning Matrigel® matrix –  the most widely used and cited extracellular matrix (ECM) –  can help streamline workflows for more efficient culturing, storing and handling.

This Teach Me in 10 will cover best practices to consider for organoid work, as well as how to use Corning Matrigel matrix and other products to support organoid models in research.

Organoid Culture Made Easy With Hilary Sherman

In this Teach Me In 10 episode we are joined by Michiel Fokkelman, head of high throughput screening at Crown Bioscience.
We will discuss the concept and definitions of high content imaging, both for 2D and 3D cell culture systems. These rich and extensive morphological readouts provide phenotypic data showing the cellular response(s) to a compound or new potential drug. Michiel then explores the use of 3D-cultured organoids and how these are utilized in drug discovery and pre-clinical drug development using high content approaches. Finally, we will then look at the role of lab automation, essential in enabling high throughput and HCI-based phenotypic screening, and how you can benefit from these technologies.

High-Throughput and High-Content Screening in Organoids and 3D Models With Michiel Fokkelman

3D cell culture systems are gaining interest in the scientific community as they provide more physiologically relevant information and more predictive in vivo data. For more than 25 years, Corning Life Sciences has delivered innovative educational tools and protocols that have advanced the science of 3D cell culture and supported the widespread adoption of these models.

In this Teach Me In 10 episode one of Corning’s customers, Dr. Joseph Regan, shares information from a recently published protocol for the isolation and functional validation of label-retaining quiescent colorectal cancer stem cells from patient-derived organoids for RNA-seq.

Isolation and Functional Validation of Quiescent Colorectal Cancer Stem Cells With Joseph Regan

Oncotarget published this trending research paper on May 11, 2022 in Volume 13, entitled, "Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation" by researchers from the Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA; Proteomics Facility, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA; UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA.

DOI - https://doi.org/10.18632/oncotarget.28228

Correspondence to - Daniel J. Donoghue - ddonoghue@ucsd.edu

Abstract

Translocation of Fibroblast Growth Factor Receptors (FGFRs) often leads to aberrant cell proliferation and cancer. The BCR-FGFR1 fusion protein, created by chromosomal translocation t(8;22)(p11;q11), contains Breakpoint Cluster Region (BCR) joined to Fibroblast Growth Factor Receptor 1 (FGFR1). BCR-FGFR1 represents a significant driver of 8p11 myeloproliferative syndrome, or stem cell leukemia/lymphoma, which progresses to acute myeloid leukemia or T-cell lymphoblastic leukemia/lymphoma. Mutations were introduced at Y177F, the binding site for adapter protein Grb2 within BCR; and at Y766F, the binding site for the membrane associated enzyme PLCγ1 within FGFR1. We examined anchorage-independent cell growth, overall cell proliferation using hematopoietic cells, and activation of downstream signaling pathways. BCR-FGFR1-induced changes in protein phosphorylation, binding partners, and signaling pathways were dissected using quantitative proteomics to interrogate the protein interactome, the phosphoproteome, and the interactome of BCR-FGFR1. The effects on BCR-FGFR1-stimulated cell proliferation were examined using the PLCγ1 inhibitor U73122, and the irreversible FGFR inhibitor futibatinib (TAS-120), both of which demonstrated efficacy. An absolute requirement is demonstrated for the dual binding partners Grb2 and PLCγ1 in BCR-FGFR1-driven cell proliferation, and new proteins such as ECSIT, USP15, GPR89, GAB1, and PTPN11 are identified as key effectors for hematopoietic transformation by BCR-FGFR1.

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Keywords - oncogenic fusion protein, chromosomal translocation, protein interactome, phosphoproteome, stem cell leukemia/lymphoma

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
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Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957

Trending With Impact: Grb2 and PLCγ1 Required in BCR-FGFR1-Driven SCLL

Harvesting your cells is an important step in maintaining healthy cultures.  Good technique will lead to a healthy single-cell suspension.  There are many harvesting options depending on the cell line and application.  In this video, we will discuss some tips and tricks for harvesting cells.

Stem Cells

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