Prostaglandin E1 and Its Analog Misoprostol Inhibit Human CML Stem Cell Self-Renewal via EP4 Receptor Activation and Repression of AP-1
Bhaskar Chanda Stem Cell Xue and colleagues show that prostaglandin E1 (PGE1) inhibits the activity and self-renewal of human CML leukemic stem cells. Combination of PGE1 or an agonist for its receptor EP4 with conventional tyrosine kinase inhibitor treatment can effectively target CML leukemic stem cells and reduce leukemia growth.
Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins
Bhaskar Chanda Stem Cell Zika virus infects neural stem cells and causes microcephaly. In this study, Yoon et al. showed that NS2A protein encoded by Zika virus, but not by Dengue virus, impairs proliferation of radial glial cells in both embryonic mouse cortex and human forebrain organoids. Mechanistically, ZIKV-NS2A disrupts adherens junction formation.
Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes
Bhaskar Chanda Stem Cell Coombs et al. examined a large cohort of solid tumor patients who underwent deep-coverage, paired tumor/blood sequencing and demonstrated that clonal hematopoiesis is common and associated with increasing age, tobacco use, and prior radiation therapy and that it predicts an increased risk of hematologic cancers and shorter survival.
Modeling of TREX1-Dependent Autoimmune Disease using Human Stem Cells Highlights L1 Accumulation as a Source of Neuroinflammation
Bhaskar Chanda Stem Cell Thomas et al. used human pluripotent stem cells to dissect the contribution of neurons and glia to the neuroinflammatory disorder Aicardi-Goutières syndrome (AGS). They found that mutant cells accumulate retroviral-like extrachromosomal nucleic acids that trigger a neurotoxic response, and they suggest that anti-retrovirals could potentially provide therapy for this disease.
Open Chromatin Profiling in hiPSC-Derived Neurons Prioritizes Functional Noncoding Psychiatric Risk Variants and Highlights Neurodevelopmental Loci
Bhaskar Chanda Stem Cell Forrest et al. outline an approach for prioritizing noncoding GWAS risk variants using open chromatin analysis in differentiating hiPSCs. They further show that CRISPR/Cas9 editing of prioritized schizophrenia risk SNPs near MIR137 alters gene expression, open chromatin, and neurodevelopment in hiPSC-derived neurons.