The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma
In this article, Singh and colleagues undertook a comparative evaluation of pre-clinical efficacy and safety of three immunotherapeutic modalities directed against CD133 braintumor-initiating cells. While all three modalities were efficacious in orthotopic GBM xenografts, CD133-specific CAR-T cells represented the most therapeutically tractable strategy against functionally important CD133+ GBM cells.
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Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease
Orlova, Bellin, Mummery, and colleagues combined three hiPSC-derived cardiac cell types in 3D microtissues. Cardiomyocytes matured structurally and functionally. Replacing healthy hiPSC-cardiac fibroblasts with patient fibroblasts recapitulated aspects of arrhythmogenic cardiomyopathy. Single-cell transcriptomics, electrophysiology, metabolomics, and ultrastructural analysis revealed roles for CX43 gap junctions and cAMP signaling in the tri-cell-type dialog.
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A Multiplexed Barcodelet Single-Cell RNA-Seq Approach Elucidates Combinatorial Signaling Pathways that Drive ESC Differentiation
Deriving stem cell differentiation protocols is time consuming and labor intensive. Yeo et al. describe a method for exploring in a single highly multiplexed experiment the combinatorial effects of up to seven signaling pathways on embryonic stem cell differentiation. An analysis framework identifies combinatorial signaling perturbations driving cells toward specific fates.
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A Non-Coding Disease Modifier of Pancreatic Agenesis Identified by Genetic Correction in a Patient-Derived iPSC Line
Kishore et al. describe using a patient iPSC line to discover and model the impact of a non-coding variant on disease penetrance. The minor allele variant of a SNP downstream of GATA6 was enriched in patients with pancreas agenesis and was shown to depress GATA6 expression in pancreas progenitors.
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Introductions to the Community: Early-Career Researchers in the Time of COVID-19
COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers.
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Disrupting Mitochondrial Copper Distribution Inhibits Leukemic Stem Cell Self-Renewal
Singh et al. demonstrate that modulating the mitochondrial intermembrane assembly (MIA) pathway leads to decreased viability of AML cells. Targeting the sulfhydryl oxidase ALR results in loss of copper chaperone COX17 and redistribution of mitochondrial copper, causing decreased DNA methylation, chromatin accessibility, and self-renewal of leukemic stem cells (LSCs).
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Patient hiPSCs Identify Vascular Smooth Muscle Arylacetamide Deacetylase as Protective against Atherosclerosis
Why some patients with type 2 diabetes are protected against cardiovascular disease (CVD) has not been clarified. Toyohara et al. reveal that in patients protected from CVD, arylacetamide deacetylase (AADAC) is elevated in vascular smooth muscle cells (VSMCs). AADAC alters lipid metabolism and cellular processes in VSMCs and ameliorates CVD.
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Integrin-Linked Kinase Mediates Therapeutic Resistance of Quiescent CML Stem Cells to Tyrosine Kinase Inhibitors
Cancer stem cells that reside in a protective niche are considered the culprit in therapy failure and relapse in most patients. Rothe et al. identified a targetable vulnerability within focal adhesions of leukemic stem cells that can resensitize these cells from therapy-resistant patients to targeted cancer therapy.
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RNA Demethylase ALKBH5 Selectively Promotes Tumorigenesis and Cancer Stem Cell Self-Renewal in Acute Myeloid Leukemia
Selectively eradicating cancer stem cells in acute myeloid leukemia (AML) remains a challenge. Shen et al. demonstrate that targeting ALKBH5, an m6A eraser, effectively inhibits AML development/maintenance and suppresses leukemia stem cell self-renewal while sparing normal hematopoiesis, highlighting the therapeutic potential of targeting the ALKBH5/m6A/TACC3 axis in treating AML.
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Leukemogenic Chromatin Alterations Promote AML Leukemia Stem Cells via a KDM4C-ALKBH5-AXL Signaling Axis
Wang et al. find that ALKBH5 is specifically required for maintaining the function of acute myeloid leukemia (AML) stem cells but not normal hematopoietic stem cells and reveal KDM4C-ALKBH5-AXL signaling axis in AML development and maintenance. These findings lay the foundation for targeting ALKBH5 for AML therapy.
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A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells
Xi et al. developed a comprehensive view of skeletal muscle and supportive cells across human development. This atlas revealed transcriptional differences among myogenic progenitors and stem cells at distinct developmental stages. This enabled identification of the developmental status of hPSC-derived muscle cells to the embryonic-to-fetal transition period in human development.
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ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress
Guallar et al. demonstrate that RNA editing by ADAR1 safeguards mesenchymal-to-epithelial transition during reprogramming. ADAR1 orchestrates cell fate decisions by limiting MDA5 sensing of double-strand-containing RNAs encoding membrane-associated proteins and, by doing so, influences the balance between ER stress/UPR and IIR in promoting somatic cell reprogramming.
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Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer
Morral and colleagues discovered that most rRNA and proteins synthesized in colorectal cancers (CRCs) are contributed by a limited subset of tumor cells that reside adjacent to the stroma. This architecture defines a common stem cell hierarchy. In some CRCs, the biosynthetic tumor cell population renders LGR5+ tumor cells dispensable.
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FASN-Dependent Lipid Metabolism Links Neurogenic Stem/Progenitor Cell Activity to Learning and Memory Deficits
Using mouse and human tissue genome engineering, Bowers et al. show that a human variant in fatty acid synthase (FASN) provides a link between altered lipid metabolism, neurogenic stem/progenitor activity, and brain function.
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Preying on Public Fears and Anxieties in a Pandemic: Businesses Selling Unproven and Unlicensed “Stem Cell Treatments” for COVID-19
In the midst of a global public health emergency, some businesses are taking advantage of widespread fears by marketing purported stem cell treatments for COVID-19. Such businesses target prospective clients with misleading claims, expose patients to potentially risky stem cell-based products, and undermine efforts to develop evidence-based treatments for COVID-19.
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Small-Molecule PAPD5 Inhibitors Restore Telomerase Activity in Patient Stem Cells
Nagpal et al. identify small-molecule inhibitors of PAPD5, a non-canonical polymerase, as regulators of the telomerase RNA component TERC. PAPD5 inhibitors restore telomere length in cells from patients with genetic “telomeropathies” and human blood stem cells xenotransplanted into mice, providing a therapeutic strategy to manipulate telomerase systemically.
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Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair
Using genetic mouse models and transcriptomic profiling, Shook et al. show that skin resident adipocytes undergo lipolysis to promote efficient macrophage inflammation after injury. Lipolysis also allows adipocyte-derived cells to dedifferentiate and generate diverse extracellular matrix-producing myofibroblasts in the wound bed.
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A Metformin-Responsive Metabolic Pathway Controls Distinct Steps in Gastric Progenitor Fate Decisions and Maturation
Mills and colleagues show that the common diabetes drug metformin activates the cellular energy hub AMP kinase (AMPK). AMPK slows mouse gastric stem cell proliferation, coaxing them to become acid-pumping parietal cells; it also promotes parietal cell mitochondria accumulation to power acid secretion. These results may explain the gastric side effects of metformin.
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Unique insight into development of the human brain: Model of the early embryonic brain (Mon, 25 May 2020)
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Image analysis technique provides better understanding of heart cell defects (Tue, 19 May 2020)
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New research into stem cell mutations could improve regenerative medicine (Thu, 14 May 2020)
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Little skates could hold the key to cartilage therapy in humans (Tue, 12 May 2020)
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Scientists show MRI predicts the efficacy of a stem cell therapy for brain injury (Tue, 12 May 2020)
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Scientists create first roadmap of human skeletal muscle development (Mon, 11 May 2020)
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More selective elimination of leukemia stem cells and blood stem cells (Fri, 08 May 2020)
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Accumulation of gene mutations in chronic Graft-versus-host disease (Thu, 07 May 2020)
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Cellular mechanism involved in Krabbe disease (Tue, 05 May 2020)
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Beta cells from stem cells: Potential for cell replacement therapy (Mon, 27 Apr 2020)
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Diabetes reversed in mice with genetically edited stem cells derived from patients (Wed, 22 Apr 2020)
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Researchers repurpose classic chemotherapy drug to overcome cancer therapy resistance (Mon, 20 Apr 2020)
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Stem cells in human embryos commit to specialization surprisingly early (Fri, 17 Apr 2020)
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Review assesses stem cell therapy potential for treating preeclampsia (Thu, 16 Apr 2020)
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COPD as a lung stem cell disease (Wed, 15 Apr 2020)
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