Stem Cells

Teach Me in 10

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

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:

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Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com

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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.

Techniques for Harvesting Adherent Cells With Hilary Sherman

For this week's episode of Teach Me in 10, we're joined by Dr.  Leonardo Ferreira, assistant professor of microbiology and immunology at the Medical University of South Carolina and the Hollings Cancer Center.  Type 1 diabetes (T1D) is the most common form of diabetes in infants and adolescents. It occurs when the immune system targets the patient’s own insulin-producing pancreatic islet cells for destruction. Right now, the only cure for T1D is a pancreas or pancreatic islet transplant. Yet, this procedure requires life-long immunosuppression to prevent immune rejection and autoimmunity. What if we could instead re-educate the patient’s immune system to accept pancreatic islets? That's the current focus of Ferreira's research, in which he is exploring the use of regulatory T cells as living drugs to treat T1D. This approach is unique in that it focuses on the root cause of the disease, immune attack of pancreatic islets, by genetically engineering human regulatory T cells to induce tolerance to pancreatic islets. He believes this line of work will help realize the promise of immune therapy for T1D, and explains how in less than 10 minutes.

Engineering Regulatory T Cells As Living Drugs With Dr. Leonardo Ferreira

For this Teach Me in 10 episode, we are joined by [url][link]https://www.wrh.ox.ac.uk/team/mara-artibani[/link][name]Dr. Mara Artibani[/name][/url], senior postdoc at the Ahmed Laboratory, Weatherall Institute of Molecular Medicine at the University of Oxford. In just 10 minutes, Dr. Artibani provides you with everything you need to know about ovarian cancer, what it is and how science can work to beat it.

Ovarian Cancer With Dr. Mara Artibani

Elixirgen Scientific

Visit our website to find out more: https://www.elixirgensci.com/

Mohamed Hassan Farah, Ph.D.
Associate Professor of Neurology, The Johns Hopkins University School of Medicine

Dr. Mohamed H. Farah is an associate professor in the department of neurology as well as the department of neuroscience at The Johns Hopkins University School of Medicine. Dr. Farah received his undergraduate degree in biochemistry from Virginia Tech in Blacksburg, Virginia. He earned his Ph.D. in neuroscience from the University of Michigan in Ann Arbor, Michigan and completed a postdoctoral fellowship in the department of pathology at The Johns Hopkins University School of Medicine. The Mohamed Farah Lab studies axonal regeneration in the peripheral nervous system. His team is currently engaged in interactions of target tissues and human axon from IPSC-derived neurons.


Muzammil Ahmad, Ph.D.
Scientist III, Elixirgen Scientific Inc.

Dr. Muzammil Ahmad joined Elixirgen Scientific in 2016. He has a Ph.D. in Biotechnology from the National Centre for Cell Science (NCSS) in India, and completed a postdoctoral fellowship at the NIH National Institute on Aging. He has over 15 years experience in the biotech and pharmaceutical research industries. Dr. Ahmad works in Research & Development at Elixirgen Scientific, where he supervises a team of Ph.D. scientists and lab assistants that develop and fine-tune commercial iPSC-derived differentiation kits for a myriad of cell types. Dr. Ahmad specializes in creating intuitive and easy-to-follow protocols to ultimately save clients’ time and increase their efficiency so they can focus on achieving their research goals.

Webinar: Human iPSC-Derived Neuromuscular Research & Transcription factor-based iPSC Differentiation

CELLSFORCELLS (C4C)

Cell-free therapy based on exosomes is witnessing a surge of published scientific papers, a rise of IP and registered clinicals trials, all driven by a swelling avidity among investors to support this transformative nanomedicine approach.

For cell-free treatment to become a reality, they need to overcome the many manufacturing hurdles posed by the large-scale production of purified exosomes.
Cells for Cells, a clinical-stage biotech company, has announced the publication of new data of its OxiumTMEXO cell culture media for increased exosome production in Frontiers in Biotechnology and Bioengineering, a specialized journal of the field. The company is part of REGENERO, the Chilean consortium for regenerative medicine supported by state funding (CORFO). In a head-to-head comparison, OxiumTMEXO outmatched the standard DMEM (starvation protocol) and a commercially available medium for exosome production. OxiumTMEXO allowed different type of cells, including the broadly used mesenchymal stem cells, to increase by 3-folds their particle production. The isolated exosomes expressed the typical pan markers while preserving their functionality both in vitro and in vivo.

Exosome technology: Downsizing Cell Therapy to Nano-Scale

Lucid Scientific

A fun whiteboard video outlining the features and benefits of the Resipher OCR device.

Learn more about the Lucid Scientific Resipher OCR Device

Aging (Aging-US)

Abstract:
Heterochronic blood sharing rejuvenates old tissues, and most of the studies on how this works focus on young plasma, its fractions, and a few youthful systemic candidates. However, it was not formally established that young blood is necessary for this multi-tissue rejuvenation. Here, using our recently developed small animal blood exchange process, we replaced half of the plasma in mice with saline containing 5% albumin (terming it a “neutral” age blood exchange, NBE) thus diluting the plasma factors and replenishing the albumin that would be diminished if only saline was used. Our data demonstrate that a single NBE suffices to meet or exceed the rejuvenative effects of enhancing muscle repair, reducing liver adiposity and fibrosis, and increasing hippocampal neurogenesis in old mice, all the key outcomes seen after blood heterochronicity. Comparative proteomic analysis on serum from NBE, and from a similar human clinical procedure of therapeutic plasma exchange (TPE), revealed a molecular re-setting of the systemic signaling milieu, interestingly, elevating the levels of some proteins, which broadly coordinate tissue maintenance and repair and promote immune responses. Moreover, a single TPE yielded functional blood rejuvenation, abrogating the typical old serum inhibition of progenitor cell proliferation. Ectopically added albumin does not seem to be the sole determinant of such rejuvenation, and levels of albumin do not decrease with age nor are increased by NBE/TPE. A model of action (supported by a large body of published data) is that significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways (with their own feedback loops) would, through changes in gene expression, have long-lasting molecular and functional effects that are consistent with our observations. This work improves our understanding of the systemic paradigms of multi-tissue rejuvenation and suggest a novel and immediate use of the FDA approved TPE for improving the health and resilience of older people.

To date, this study has generated an Altmetric Attention Score of 140. The Altmetric Attention Score provides an at-a-glance indication of the volume and type of online attention the research has received. 

Top Aging publications rated by Altmetric score -  https://www.aging-us.com/news_room/altmetric

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.103418

DOI - https://doi.org/10.18632/aging.103418

Full text - https://www.aging-us.com/article/103418/text

Correspondence to: Irina M. Conboy email: iconboy@berkeley.edu

Keywords: blood exchange, therapeutic plasma exchange, multi-tissue rejuvenation, rejuvenation by dilution


About Aging

Launched in 2009, Aging 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 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 http://www.Aging-US.com or connect with us on:

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Aging is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

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