Reconstruction of the Human Blood-Brain Barrier In Vitro Reveals a Pathogenic Mechanism of APOE4 in Pericytes

Researchers revealed the role of pericytes in apolipoprotein (APOE4)-mediated cerebral amyloid angiopathy (CAA) and highlighted calcineurin-nuclear factor of activated T cells signaling as a therapeutic target in CAA and Alzheimer’s disease.
[Nature Medicine]
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TETs Compete with DNMT3 Activity in Pluripotent Cells at Thousands of Methylated Somatic Enhancers

Investigators analyzed the independent and combined effects of positive DNMT3A/B and negative TET1-3 regulators on the DNA methylation landscape using a panel of knockout human ESC lines.
[Nature Genetics]
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Alzheimer’s-Associated PLCγ2 Is a Signaling Node Required for Both TREM2 Function and the Inflammatory Response in Human Microglia

The authors used genetically engineered human iPSC-derived microglia-like cells to show that triggering receptor expressed on myeloid cells 2 (TREM2) signaled through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
[Nature Neuroscience]
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Synergistic Gene Editing in Human iPS Cells via Cell Cycle and DNA Repair Modulation

Scientists established a fluorescent DNA repair assay in human iPSCs to visualize and quantify the frequency of DNA repair outcomes during monoallelic and biallelic targeting.
[Nature Communications]
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N-3 Polyunsaturated Fatty Acids Promote Astrocyte Differentiation and Neurotrophin Production Independent of cAMP in Patient-Derived Neural Stem Cells

iPSC-derived neuronal stem cell lines were generated from individuals with major depressive disorder. Astrocytes differentiated from patient-derived neuronal stem cells were verified by GFAP and cells were treated with eicosapentaenoic acid, docosahexaenoic acid or stearic acid.
[Molecular Psychiatry]
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Hippo-Yap Signaling Controls Lineage Differentiation of Mouse Embryonic Stem Cells through Modulating the Formation of Super-Enhancers

Investigators found that knockout of Mst1 and Mst2, two key components of the Hippo signaling in mouse ESCs, resulted in a disruption of differentiation into mesendoderm lineage. They revealed a novel mechanism on how the Hippo-YAP signaling pathway dictated ESC lineage differentiation.
[Nucleic Acids Research]
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Acute Myeloid Leukemia iPSCs Reveal a Role for RUNX1 in the Maintenance of Human Leukemia Stem Cells

Researchers report that genetically clonal iPSCs derived from an acute myeloid leukemia patient and characterized by exceptionally high engraftment potential gave rise, upon hematopoietic differentiation, to a phenotypic hierarchy.
[Cell Reports]
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Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells

Improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, investigators generated functional engineered human mini-livers and performed transplantation in a rat model.
[Cell Reports]
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Prevention of Tumor Risk Associated with the Reprogramming of Human Pluripotent Stem Cells

The authors focus on the risk of tumor formation by human PSCs, and on the possible treatment options if it occurs. Potential new techniques that target epigenetic processes and chromatin regulation provide opportunities for human cancer modeling and regenerative medicine.
[Journal of Experimental & Clinical Cancer Research]
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International Prize Awarded to Two Pieces of Novel Research in the 3Rs

The 2019 3Rs prize has been jointly awarded to Dr Francesca Nunn and Dr Marta Shahbazi. Marta and colleagues have developed advanced 3D cultures of human and mouse ESCs to mimic the development of the embryo at implantation and the subsequent morphogenesis and formation of the amniotic cavity.
[EurekAlert!]
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Improving the Safety of Human Pluripotent Stem Cell Therapies Using Genome-Edited Orthogonal Safeguards

Scientists used genome editing to engineer a general platform to improve the safety of future human pluripotent stem cell-derived cell transplantation therapies.
[Nature Communications]
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