Identification and Massively Parallel Characterization of Regulatory Elements Driving Neural Induction
To reveal regulatory dynamics during neural induction, we performed RNA-seq, ChIP-seq, ATAC-seq, and lentiMPRA at seven time points during early neural differentiation. We incorporated all information and identified TFs that play important roles in this process. We demonstrated overexpression or CRISPRi of five TFs affected ESC-NPC differentiation.
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Sphingolipid Modulation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal
Lipid metabolism is distinctly regulated in human hematopoietic stem cells (HSCs) versus progenitors. Xie et al. profiled the sphingolipidome in human cord blood and show that modulating sphingolipids during the transition from quiescence to cellular activation in ex vivo culture induced proteostatic cellular stress programs to maintain HSC self-renewal.
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Single-Cell Transcriptome Analysis of Uniparental Embryos Reveals Parent-of-Origin Effects on Human Preimplantation Development
Leng et al. performed a comprehensive survey of transcriptional activities between biparental and uniparental embryos by single-cell RNA sequencing. They provide insights into the critical features of parental genome activation before implantation and help elucidate parent-of-origin effects in early human development.
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The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis
P-bodies are cytoplasmic RNP granules whose role in stem cells remains largely elusive. Di Stefano et al. show that the disruption of P-bodies upon loss of DDX6 perturbs the self-renewal and differentiation of various stem cell populations through translational upregulation of cell fate regulators and profound rewiring of chromatin landscapes.
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PRDM16 Maintains Homeostasis of the Intestinal Epithelium by Controlling Region-Specific Metabolism
Metabolic program expression and dependency vary along the length of the small intestine. PRDM16 transcriptionally regulates fatty acid oxidation (FAO), which is highest in the upper small intestine. Loss of Prdm16 reduces FAO, leading to apoptosis and diminished epithelial differentiation of progenitor cells in the upper intestine.
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Asymmetric Centromeres Differentially Coordinate with Mitotic Machinery to Ensure Biased Sister Chromatid Segregation in Germline Stem Cells
Drosophila male germline stem cell undergoes asymmetric cell division to produce two different cells. Ranjan et al. show that a temporal asymmetry of microtubules tightly coordinates with quantitative asymmetries in sister centromeres and sister kinetochores to ensure non-random sister chromatids segregation and asymmetric epigenetic inheritance, which regulate distinct cell fates.
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NHEJ-Mediated Repair of CRISPR-Cas9-Induced DNA Breaks Efficiently Corrects Mutations in HSPCs from Patients with Fanconi Anemia
NHEJ is an error-prone DSB repair mechanism typically exploited to create gene knockouts. Román-Rodríguez and colleagues show efficient CRISPR-Cas9-mediated repair of mutated Fanconi anemia genes using NHEJ to generate compensatory mutations that correct the phenotype of FA patient HSCs, suggesting a simple and feasible clinical approach for monogenic hematopoietic diseases.
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Wnt4 from the Niche Controls the Mechano-Properties and Quiescent State of Muscle Stem Cells
Eliazer et al. identified a muscle-fiber-derived niche factor, Wnt4, that maintains SC quiescence. Wnt4 acts in a paracrine manner, signaling through the non-canonical Rho-GTPase pathway to maintain tension and quiescence of SCs. After injury, Wnt4-Rho signaling decreases rapidly, leading to changes in mechano-properties that precede cell-cycle entry.
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Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation
In murine hematopoietic Stag2 deletion, Stag1 rescues topologically associated domains in the absence of Stag2 but cannot restore the chromatin architecture required for hematopoietic lineage commitment. PU.1 target genes lose accessibility and expression. Induced target gene expression, but not PU.1 overexpression, is sufficient to restore differentiation in the altered chromatin state.
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A compound effective to chemotherapy-resistant cancer cells identified (Fri, 18 Oct 2019)
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When added to gene therapy, plant-based compound may enable faster, more effective treatments (Thu, 17 Oct 2019)
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Embryo's early development revealed in a dish (Thu, 17 Oct 2019)
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Viagra shows promise for use in bone marrow transplants (Thu, 10 Oct 2019)
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First cell map of developing human liver reveals how blood and immune system develops (Wed, 09 Oct 2019)
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Potential liver cancer treatment by targeting cancer stem-like cells (Wed, 09 Oct 2019)
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Treatment for 'low T' could someday come from a single skin cell (Mon, 07 Oct 2019)
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Stem cell studies offer hope for childhood neurological condition (Thu, 03 Oct 2019)
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New method to purify cell types to high purity (Thu, 03 Oct 2019)
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Possible therapeutic target for slow healing of aged muscles (Mon, 30 Sep 2019)
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How time affects the fate of stem cells (Thu, 26 Sep 2019)
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Engineered killer T cells could provide long-lasting immunity against cancer (Tue, 24 Sep 2019)
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New insight as to how cells maintain their identity (Fri, 20 Sep 2019)
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Suntanner, heal thyself: Exosome therapy may enable better repair of sun, age-damaged skin (Thu, 19 Sep 2019)
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Gene editing enables researchers to correct mutation in muscle stem cells in DMD model (Tue, 17 Sep 2019)
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