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ETV7 limits the antiviral and antitumor efficacy of CD8 T cells by diverting their fate toward exhaustion.
Nat Cancer
January 2025
State Key Laboratory of Molecular Oncology, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
Terminal exhaustion is a critical barrier to antitumor immunity. By integrating and analyzing single-cell RNA-sequencing and single-cell assay for transposase-accessible chromatin with sequencing data, we found that ETS variant 7 (ETV7) is indispensable for determining CD8 T cell fate in tumors. ETV7 introduction drives T cell differentiation from memory to terminal exhaustion, limiting antiviral and antitumor efficacy in male mice.
View Article and Find Full Text PDFGeneration of a PDK-1 knockout human embryonic stem cell line by CRISPR/(WAe009-A-2K) Cas9 editing.
Stem Cell Res
December 2024
Anzhen Hospital, Capital Medical University, Beijing 100029, China; Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China. Electronic address:
Pyruvate Dehydrogenase Kinase1 (PDK1) belongs to the family of kinases, regulates diverse metabolic processes. PDK1 is a susceptibility locus for heart failure via thinning of ventricle walls, and enlarged atria and ventricles. We successfully developed a PDK1 knockout (PDK1/) human embryonic stem cell (hESC) line using an episomal vector-based CRISPR/Cas9 system explore the role of PDK in human heart development.
View Article and Find Full Text PDFA rapid chemical reprogramming system to generate human pluripotent stem cells.
Nat Chem Biol
January 2025
MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences and MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Chemical reprogramming enables the generation of human pluripotent stem (hCiPS) cells from somatic cells using small molecules, providing a promising strategy for regenerative medicine. However, the current method is time consuming, and some cell lines from different donors are resistant to chemical induction, limiting the utility of this approach. Here, we developed a fast reprogramming system capable of generating hCiPS cells in as few as 10 days.
View Article and Find Full Text PDFOrthogonal RNA replication enables directed evolution and Darwinian adaptation in mammalian cells.
Nat Chem Biol
January 2025
Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Directed evolution in mammalian cells offers a powerful approach for advancing synthetic biology applications. However, existing mammalian-based directed evolution methods face substantial bottlenecks, including host genome interference, small library size and uncontrolled mutagenesis. Here we engineered an orthogonal alphaviral RNA replication system to evolve RNA-based devices, enabling RNA replicase-assisted continuous evolution (REPLACE) in proliferating mammalian cells.
View Article and Find Full Text PDFNanobody-assisted nanoluciferase fragment complementation for in situ measurement and visualization of endogenous protein-protein interaction.
Biosens Bioelectron
March 2025
Shenzhen Bay Laboratory, Shenzhen, 518132, China. Electronic address:
Here, we developed nanobody-assisted nanoluciferase fragment complementation for in situ measurement and visualization of endogenous protein-protein interaction (NanaPPI). When an interaction occurs, primary antibodies for two proteins bring the proximity of secondary nanobody-fused small/large fragment to reassemble into an intact NanoLuc variant, thus transforming interaction events to luminescent signals in situ with high sensitivity. Compared to proximity ligation assay, NanaPPI has a similar signal-to-background ratio, but it is more convenient with faster procedures, easier readout and lower cost.
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