Lineage Tracing Reveals a Subset of Reserve Muscle Stem Cells Capable of Clonal Expansion under Stress
Brack and colleagues identify a muscle reserve stem cell population marked by Mx1-Cre and Pax3 within the Pax7+ satellite cell pool. After radiation, reserve stem cells clonally expand to become the dominant stem cell population for repair and stem cell maintenance. ROS levels across the satellite cell pool endow radiotolerance.
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PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress
Der Vartanian and colleagues identify a functional heterogeneity of skeletal muscle stem cell response to environmental stress. While PAX3-negative muscle stem cells display impaired survival, aberrant activation, and sporadic fusion to myofibers upon TCDD exposure, PAX3-positive muscle stem cells are protected against the pollutant through an mTORC1-dependent G(alert) response.
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Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs
Transposable elements (TEs) are key to the evolutionary turnover of regulatory sequences but potentially toxic to the host. Trono and colleagues demonstrate that KRAB zinc-finger proteins tame the activity of TEs during human early embryogenesis, thus allowing for their genome-wide incorporation into species-specific transcriptional networks.
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Spatially Restricted Stromal Wnt Signaling Restrains Prostate Epithelial Progenitor Growth through Direct and Indirect Mechanisms
Wei et al. show that human and mouse prostate stromal cells exhibit region-specific differences in Wnt ligand expression and Wnt/β-catenin activity. Canonical and non-canonical Wnt signaling cooperate to restrain prostate stem or progenitor activity through direct and indirect TGFβ-dependent pathways.
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Single-Cell Transcriptomics Uncovers Glial Progenitor Diversity and Cell Fate Determinants during Development and Gliomagenesis
By applying lineage-targeted, single-cell transcriptomics analysis, Weng and colleagues uncover distinct intermediate glial progenitors in the neonatal brain and their malignant counterparts in murine and human gliomas. Lineage-driving network analysis further identifies Zfp36l1 as a pivotal regulator for glial fate specification and glioma growth.
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Modeling the Pathological Long-Range Regulatory Effects of Human Structural Variation with Patient-Specific hiPSCs
Elucidating the long-range pathomechanisms of structural variants in vivo is often difficult due to differences in gene dosage sensitivity between mice and humans. Laugsch et al. combined neural crest cells derived from patient-specific hiPSCs and functional genomics to demonstrate that an inversion causes BOFS by disconnecting TFAP2A from its enhancers.
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Drug Screening in Human PSC-Cardiac Organoids Identifies Pro-proliferative Compounds Acting via the Mevalonate Pathway
Hudson, Porrello, et al. perform drug screening in human mini-hearts to identify compounds that promote human heart muscle cell proliferation. Drug screening also eliminated potential side effects on heart rhythm and function. Induction of heart muscle cell proliferation required activation of the cholesterol biosynthesis pathway.
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Mesenchymal Niche-Specific Expression of Cxcl12 Controls Quiescence of Treatment-Resistant Leukemia Stem Cells
Leukemia stem cells (LSCs) resist elimination by tyrosine kinase inhibitor (TKI) treatment. Bhatia and colleagues report that CXCL12 deletion from mesenchymal stromal cells (MSCs) reduces LSC colocalization, enhances LSC cycling, and increases LSC elimination by TKI treatment, indicating that CXCL12-expressing MSC niches are critical for maintaining quiescent, TKI-resistant LSCs.
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A Human iPSC Double-Reporter System Enables Purification of Cardiac Lineage Subpopulations with Distinct Function and Drug Response Profiles
Wu and colleagues create a double-knockin human TBX5Clover2 and NKX2-5TagRFP reporter to delineate cardiac lineages during differentiation. Molecular and functional analyses uncover that differential expression of TBX5 and NKX2-5 specifies different cardiac fate. This reporter is applicable for studying cardiac lineage determination in vitro and isolating cardiac subpopulations.
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Single-Cell Proteomics Reveal that Quantitative Changes in Co-expressed Lineage-Specific Transcription Factors Determine Cell Fate
Brand and colleagues used CyTOF with temporal barcoding and quantitative mass spectrometry to reconstitute a trajectory of human erythropoiesis. By measuring endogenous TF protein levels in single cells over time, they show that TFs from competing lineages are co-expressed in bipotential progenitors, and changes in their abundance underlie cell fate decisions.
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Factors behind embryonic stem cell state (Wed, 17 Apr 2019)
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A light-activated remote control for cells (Wed, 17 Apr 2019)
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Boosting muscle stem cells to treat muscular dystrophy and aging muscles (Wed, 17 Apr 2019)
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Scientists 'reverse engineer' brain cancer cells to find new targets for treatment (Tue, 16 Apr 2019)
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How inflammation causes gastric cancer (Tue, 16 Apr 2019)
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Discovery of 'kingpin' stem cell may help in the understanding of cancerous tumors (Thu, 11 Apr 2019)
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Shutting down deadly pediatric brain cancer at its earliest moments (Thu, 11 Apr 2019)
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Human iPSC-derived MSCs from aged individuals acquire a rejuvenation signature (Wed, 10 Apr 2019)
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Mutation stands in the way of healthy blood cell maturation (Fri, 05 Apr 2019)
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Genome-wide analysis reveals new strategies to target pancreatic cancer (Thu, 04 Apr 2019)
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A step toward recovering reproduction in girls who survive childhood cancer (Wed, 03 Apr 2019)
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A soft spot for stem cells helps cornea healing (Wed, 03 Apr 2019)
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Transplanted bone marrow endothelial progenitor cells delay ALS disease progression (Tue, 02 Apr 2019)
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People can survive organ failure, a review explores how (Fri, 29 Mar 2019)
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Researchers optimize gene editing for SCD and beta thalassemia (Thu, 28 Mar 2019)
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