CRISPR-Based Adenine Editors Correct Nonsense Mutations in a Cystic Fibrosis Organoid Biobank
Here, we show the generation of an extensive cystic fibrosis patient-derived intestinal organoid biobank. We use this biobank to study gene correction by adenine base editors and show genetic repair of four selected nonsense mutations in CFTR without any genome-wide off-target effects on canonical and non-canonical PAMs.
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Distinct Mesenchymal Cell Populations Generate the Essential Intestinal BMP Signaling Gradient
Sub-epithelial mesenchyme generates signal gradients that sustain intestinal stem cells (ISCs). McCarthy and colleagues show that anatomically and functionally distinct cells produce the BMP gradient: telocytes predominate at the crypt-villus junction and express abundant BMPs, whereas trophocytes lie near ISCs at the crypt base and express the BMP inhibitor Grem1.
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Ascl2-Dependent Cell Dedifferentiation Drives Regeneration of Ablated Intestinal Stem Cells
Quiescent reserve “+4 crypt cells” are thought to be a major source for recovery of ablated intestinal stem cells. Shivdasani et al. show instead that recovery occurs almost exclusively by dedifferentiation of recent stem cell progeny, which requires the transcription factor ASCL2 for this restorative potential.
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Reconstructed Single-Cell Fate Trajectories Define Lineage Plasticity Windows during Differentiation of Human PSC-Derived Distal Lung Progenitors
Hurley et al. show that a combination of single-cell transcriptomics, computational modeling, and DNA barcoding can map cell-fate trajectories, predicting signaling pathways, transcription factors, and the time of activation for optimizing cell fate, as pluripotent stem cell-derived lung progenitors differentiate toward self-renewing lung alveolar epithelial cells.
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Interneuron Accumulation of Phosphorylated tau Impairs Adult Hippocampal Neurogenesis by Suppressing GABAergic Transmission
Impaired adult hippocampal neurogenesis contributes to the cognitive decline in Alzheimer’s disease. Zheng et al. report that phospho-tau accumulation in dentate gyrus GABAergic interneurons disrupts adult hippocampal neurogenesis and increased astrogliosis. Importantly, strengthening GABAergic signaling can rescue neurogenesis and improve cognitive functions in mouse models of Alzheimer’s disease.
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Distinct Airway Epithelial Stem Cells Hide among Club Cells but Mobilize to Promote Alveolar Regeneration
Through single-cell transcriptomic profiling of distal lung airway epithelium, Kathiriya et al. reveal rare progenitors that activate and mobilize after injury to help re-establish alveolar lining and barrier function. The findings favor expansion of pre-existing stem cells over widespread de-differentiation of mature cells as a major pathway of lung regeneration.
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Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition
Hinge et al. show that mitochondria are permanently remodeled after HSC division despite re-entry into quiescence. HSCs keep dysfunctional mitochondria through asymmetric segregation during mitosis, which does not prevent reversible HSC quiescence and cell cycle progression but drives their functional decline via asynchrony in the cell cycle and biosynthetic gene expression.
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Viral Delivery of GDNF Promotes Functional Integration of Human Stem Cell Grafts in Parkinson’s Disease
Gantner et al. provide preclinical evidence that the timely overexpression of glial cell-derived neurotrophic factor (GDNF) within the host brain can promote the maturation, plasticity, and functional integration of human stem cell-derived dopamine grafts in a rodent model of Parkinson’s disease.
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Embryonic Barcoding of Equipotent Mammary Progenitors Functionally Identifies Breast Cancer Drivers
Ying and Beronja employ lentiviral targeting and quantitative lineage tracing of murine mammary epithelium to establish that early progenitors are bi-potent and with equal long-term growth potential. Using these insights, they design a large-scale genetic screen that can identify functional drivers of tumor initiation and subtype shift in breast cancer.
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Computer simulations visualize how DNA converts cells into stem cells (Fri, 14 Feb 2020)
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Scientists discover how rogue communications between cells lead to leukemia (Thu, 06 Feb 2020)
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Abnormal bone formation after trauma explained and reversed in mice (Thu, 06 Feb 2020)
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New hydrogels wither while stem cells flourish for tissue repair (Tue, 04 Feb 2020)
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Scientists boost gene-editing tools to new heights in human stem cells (Thu, 30 Jan 2020)
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Molecular motors direct the fate of stem cells (Wed, 29 Jan 2020)
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New injection technique may boost spinal cord injury repair efforts (Wed, 29 Jan 2020)
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After a bone injury, shape-shifting cells rush to the rescue (Wed, 29 Jan 2020)
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Six patients with rare blood disease are doing well after gene therapy clinical trial (Wed, 29 Jan 2020)
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First treatment for pain using human stem cells a success (Thu, 23 Jan 2020)
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Solving a biological puzzle: How stress causes gray hair (Wed, 22 Jan 2020)
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Cancer study may accidentally help researchers create usable blood stem cells (Thu, 16 Jan 2020)
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Mutations in donors' stem cells may cause problems for cancer patients (Wed, 15 Jan 2020)
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Artificial muscle sheets transform stem cells into bone (Mon, 13 Jan 2020)
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First genomic study of puberty yields insights into development and cancer (Fri, 10 Jan 2020)
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