Archive | March 2017

DUSP9 Modulates DNA Hypomethylation in Female Mouse Pluripotent Stem Cells

Bhaskar Chanda Stem Cell The molecular equivalence of ESCs and EGCs remains incompletely understood. Choi et al. show that ESCs and EGCs are highly similar and that sex rather than cell type drives the transcriptional and epigenetic differences observed between individual cell lines. Female-specific hypomethylation is partially due to upregulation of the X-linked MAPK phosphatase DUSP9.

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H3K4 Methylation-Dependent Memory of Somatic Cell Identity Inhibits Reprogramming and Development of Nuclear Transfer Embryos

Bhaskar Chanda Stem Cell Hörmanseder et al. find that persistent memories of transcriptional activity in donor cell identity genes present a barrier to cell-fate reprogramming following nuclear transfer. They show that reducing H3K4 methylation in donor cells reduces transcriptional memory and improves the development of embryos derived by nuclear transfer.

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Efficient Derivation of Functional Human Airway Epithelium from Pluripotent Stem Cells via Temporal Regulation of Wnt Signaling

Bhaskar Chanda Stem Cell Kotton and colleagues show that carefully timed regulation of Wnt signaling can direct human pluripotent cells to differentiate rapidly into functional airway epithelial organoids with many potential applications in disease modeling, drug screening, and precision medicine, and for diseases such as cystic fibrosis.

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Comprehensive Cell Surface Protein Profiling Identifies Specific Markers of Human Naive and Primed Pluripotent States

Bhaskar Chanda Stem Cell Collier et al. use profiling to identify cell surface proteins that are specific for naive versus primed human pluripotent cells and then use them to isolate and characterize live naive cells arising during primed-to-naive resetting.

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Single-Cell 5-Formylcytosine Landscapes of Mammalian Early Embryos and ESCs at Single-Base Resolution

Bhaskar Chanda Stem Cell CLEVER-seq is a single-cell, single-base resolution whole-genome 5fC-sequencing technology. CLEVER-seq reveals intrinsic 5fC heterogeneity in mouse early embryos, EpiSCs, and ESCs and dissects its highly patterned genomic distributions. During mouse pre-implantation development, 5fC shows parental-specific signatures, and promoter 5fC production precedes the upregulation of corresponding gene expression.

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Amitosis of Polyploid Cells Regenerates Functional Stem Cells in the Intestine

Bhaskar Chanda Stem Cell Lucchetta and Ohlstein describe an unexpected mechanism of stem cell replacement in the Drosophila intestine. They found that in some situations where many stem cells are lost, they can be replaced through a process of ploidy reduction, or amitosis, of differentiated polyploid cells to regenerate functional stem cells.

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Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration

Bhaskar Chanda Stem Cell Ambrosi, Schulz, and colleagues define a stem cell-like population that gives rise to osteogenic progeny and promotes hematopoietic reconstitution. Aging and high-fat diet reprogram the mesenchymal lineage to preferentially give rise to adipogenic cells that impair reconstitution and bone fracture healing. Bone tissue repair is fully restored by DPP4 inhibition.

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Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells

Bhaskar Chanda Stem Cell Lgr5+ intestinal stem cells are considered to be a homogeneous and rapidly proliferating population. Barriga et al. show that the RNA binding protein Mex3a defines a subset of slowly proliferating Lgr5+ cells that contribute to all intestinal lineages with slow kinetics, are resistant to chemotherapy, and support intestinal regeneration.

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PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation

Bhaskar Chanda Stem Cell Cruz-Molina et al. demonstrate that pluripotent-associated poised enhancers are necessary for the induction of anterior neural genes. Poised enhancers physically interact with their target genes in embryonic stem cells in a PRC2-dependent manner. Thus, polycomb proteins might facilitate neural induction by providing anterior neural loci with a permissive regulatory topology.

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Targeting BMI1 Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma

Bhaskar Chanda Stem Cell Chen et al. show that BMI1+ CSCs drive invasive growth and cervical lymph node metastasis in squamous cell carcinoma. BMI1+ CSCs have increased AP-1 activity and are chemotherapy resistant, and combination therapy that targets BMI1+ CSCs and the tumor bulk yields better outcomes and effectively eliminates metastasis.

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