Phenotypic Plasticity: Driver of Cancer Initiation, Progression, and Therapy Resistance
Gupta et al. discuss how cells acquire plasticity and the role of plasticity in initiating cancer, cancer progression, and metastasis and in developing therapy resistance. The article also highlights the epithelial-to-mesenchymal transition (EMT) and known molecular mechanisms underlying plasticity, and it considers potential therapeutic avenues.
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yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs
De novo DNA methylation facilitates the stabilization of cellular identities during embryogenesis, while loci encoding regulators of developmental cell fate decisions remain hypomethylated. Frank et al. reveal a long non-coding-RNA-mediated regulatory layer essential for safeguarding these loci from aberrant DNA methylation.
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Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool
Fu et al. demonstrate the presence and multilineage differentiation potential of hematopoietic stem and progenitor cells (HSPCs) carried in human intestinal allografts. These contribute to peripheral blood mixed chimerism in the recipient. Kinetic turnover studies revealed the gradual replacement of intestinal mucosal HSPCs by a circulating pool in humans.
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Mesenchymal Precursor Cells in Adult Nerves Contribute to Mammalian Tissue Repair and Regeneration
Carr et al. demonstrate that peripheral nerves contain mesenchymal precursor-like cells that participate in repair of damaged mesenchymal tissues. Utilizing scRNA-seq, lineage tracing, and transplantation approaches, the authors show that neural crest-derived endoneurial mesenchymal precursor cells generate bone and dermal cells during digit tip regeneration and skin wound healing.
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Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes
Bulk and single-cell RNA-seq of iPSC-derived dopamine neurons from control and PD GBA-N370S patients stratified a clinically distinct patient and revealed HDAC4 as a potential therapeutic PD target. Pharmacological modulation of HDAC4 rescued PD-related phenotypes in GBA-N370S neurons. HDAC4 perturbation was also observed in a subset of sporadic PD patients.
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Integrative Proteomic Profiling Reveals PRC2-Dependent Epigenetic Crosstalk Maintains Ground-State Pluripotency
Marks and colleagues use integrative mass spectrometry to profile post-translational histone modifications and the chromatin-associated proteome in ground-state pluripotency. This reveals H3K27me3 and PRC2 as widespread hallmarks on euchromatin and heterochromatin. They show that ubiquitous chromatin-associated PRC2 protects the epigenome from priming, in particular from gaining DNA methylation.
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IKZF2 Drives Leukemia Stem Cell Self-Renewal and Inhibits Myeloid Differentiation
Park et al. find that IKZF2 regulates chromatin accessibility of self-renewal and differentiation genes in leukemic stem cells. Depletion of IKZF2 has preferential effect in leukemic stem cells compared to normal hematopoietic stem cells, providing a new strategy for targeting leukemic stem cells.
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Quantitative Clonal Analysis and Single-Cell Transcriptomics Reveal Division Kinetics, Hierarchy, and Fate of Oral Epithelial Progenitor Cells
Jones et al. define the organization, cycling kinetics, and clonal dynamics of oral mucosal progenitor cells. They also show, via single-cell RNA sequencing, that the basal layer contains progenitor and post-mitotic cells at various stages of maturation, demonstrating basal layer heterogeneity and providing insights into localization of cell fate decisions.
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Deterministic Somatic Cell Reprogramming Involves Continuous Transcriptional Changes Governed by Myc and Epigenetic-Driven Modules
The epigenetic dynamics of iPSC reprogramming in correctly reprogrammed cells at high-resolution remain largely undefined. Hanna and colleagues now provide comprehensive characterization during the entire course of murine fibroblast reprogramming, by using Gatad2a-Mbd3/NuRD-depleted and radically efficient reprogramming systems. These data provide insights into key questions underlying successful naive iPSC reprogramming.
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Human ESC-Derived Chimeric Mouse Models of Huntington’s Disease Reveal Cell-Intrinsic Defects in Glial Progenitor Cell Differentiation
The authors show that glial progenitor cells derived from human ESCs expressing mutant Huntingtin (mHTT) are delayed and defective in their maturation; their suppressed transcription of differentiation-associated genes leads to both astrocytic dysfunction and myelin deficiency in vivo. Glial pathology may thus contribute to disease phenotype in Huntington’s disease.
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Can stem cells help a diseased heart heal itself? Researcher achieves important milestone (Fri, 14 Dec 2018)
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The immune system's supercell -- how it matures (Thu, 13 Dec 2018)
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Stem cell researchers develop promising technique to generate new muscle cells in lab (Wed, 12 Dec 2018)
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New method for studying ALS more effectively (Wed, 12 Dec 2018)
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Maintaining the unlimited potential of stem cells (Wed, 12 Dec 2018)
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The source of stem cells points to two proteins (Tue, 11 Dec 2018)
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Potential seen for tailoring treatment for acute myeloid leukemia (Fri, 07 Dec 2018)
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Sea invertebrate sheds light on evolution of human blood, immune systems (Wed, 05 Dec 2018)
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New research on stem cell transplantation for myeloid cancers (Mon, 03 Dec 2018)
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Some blood cells have a surprising source: Your gut (Thu, 29 Nov 2018)
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Next step towards replacement therapy in type 1 diabetes (Wed, 28 Nov 2018)
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Platelets grown from stem cells may be alternative to donated platelets (Wed, 28 Nov 2018)
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Healthy blood stem cells have as many DNA mutations as leukemic cells (Wed, 28 Nov 2018)
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Citrate-based biomaterial fuels bone healing with less rejection (Mon, 26 Nov 2018)
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Underlying mechanisms of 3d tissue formation (Wed, 21 Nov 2018)
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