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Updated: 12 hours 38 min ago

Myofibroblasts Derived from Hepatic Progenitor Cells Create the Tumor Microenvironment

Thu, 12/01/2016 - 00:00
In this article, Suzuki and colleagues found that hepatic progenitor cells (HPCs) have a potential for trilineage differentiation into hepatocytes, cholangiocytes, and myofibroblasts. Although the frequency of myofibroblast production from HPCs is low in culture, HPCs can give rise to a number of myofibroblasts during tumor development and contribute to the formation of the tumor microenvironment.

Inhibiting the SUMO Pathway Represses the Cancer Stem Cell Population in Breast and Colorectal Carcinomas

Thu, 12/01/2016 - 00:00
Weigel and colleagues provide substantial evidence for developing cancer stem cell-specific therapy based on inhibiting the SUMO pathway. They show that inhibition of sumoylation enzymes by knockdown or small-molecule inhibitors repressed cancer stem cells with loss of CD44 and MMP14, and reduced invasiveness and inhibition of tumor growth. Common SUMO-sensitive mechanisms were dependent upon TFAP2A in breast and colon cancer.

p53 and p73 Regulate Apoptosis but Not Cell-Cycle Progression in Mouse Embryonic Stem Cells upon DNA Damage and Differentiation

Thu, 11/17/2016 - 00:00
In this article, Xiao, Li, and colleagues show that p53 and p73 are pivotal for DNA-damage-induced apoptosis but not for G2/M arrest in mESCs. In addition, doxorubicin induces RB via p53-mediated suppression of miR-17-92 and miR-106a-363. During differentiation, p73, but not p53, is induced, and both p53 and p73 are critical for differentiation-induced apoptosis.

PRDM14 Drives OCT3/4 Recruitment via Active Demethylation in the Transition from Primed to Naive Pluripotency

Thu, 11/17/2016 - 00:00
In this article, Seki and colleagues exploit an in vitro differentiation system of epiblast-like cells (EpiLCs) from embryonic stem cells (ESCs) to investigate the function of PRDM14. Overexpression of PRDM14 in EpiLCs induces the conversion from EpiLCs to ESCs through active DNA demethylation-mediated OCT3/4 recruitment at pluripotent genes in adherent culture.

PAR1 Scaffolds TGFβRII to Downregulate TGF-β Signaling and Activate ESC Differentiation to Endothelial Cells

Thu, 11/17/2016 - 00:00
In this article, Malik and colleagues show that the G-protein-coupled receptor PAR1 can act as a scaffold for the TGF-β receptor TGFβRII and thereby suppress downstream TGF-β signaling in embryonic stem cells undergoing endothelial differentiation. Thus, PAR1 functions as a rheostat controlling TGF-β signaling and the generation of functional endothelial cells from embryonic stem cells.

In Vitro Models of GJB2-Related Hearing Loss Recapitulate Ca2+ Transients via a Gap Junction Characteristic of Developing Cochlea

Thu, 11/10/2016 - 00:00
Kamiya and colleagues generated functional CX26-gap junction plaque-forming cells from iPSCs. These cells exhibited spontaneous ATP- and hemichannel-mediated Ca2+ transients typical of the developing cochlea. Furthermore, an in vitro disease model from CX26-deficient deafness mice recapitulated the drastic disruption of gap junction plaques reported to be the primary pathology of GJB2-related hearing loss.

CGG Repeat-Induced FMR1 Silencing Depends on the Expansion Size in Human iPSCs and Neurons Carrying Unmethylated Full Mutations

Thu, 11/10/2016 - 00:00
Rare individuals do not silence FMR1 and do not develop FXS despite carrying the disease causing CGG expansion. Using iPSCs, Fodor, Di Giorgio, and colleagues show that these individuals have not lost the ability to silence FMR1 but the CGG repeat number required for silencing is higher than the one described for FXS patients.

Detecting Genetic Mosaicism in Cultures of Human Pluripotent Stem Cells

Tue, 11/08/2016 - 00:00
Barbaric and colleagues tested how many metaphases need to be scored to detect different levels of mosaicism in hPSC cultures. They also devised qPCR assays as a rapid means of detecting common chromosomal abnormalities. Testing of the sensitivity of qPCR, digital droplet PCR, and FISH revealed that these methods can miss as many as 10% abnormal cells in the population.

CITED2 Cooperates with ISL1 and Promotes Cardiac Differentiation of Mouse Embryonic Stem Cells

Thu, 11/03/2016 - 00:00
In this article, Bragança and colleagues show that the transcriptional regulator Cited2 is essential for cardiac commitment of mouse embryonic stem cells (ESC), and its depletion in ESC impairs the expression of early mesoderm markers and cardiogenic transcription factors. In addition, they demonstrate that CITED2 and ISL1 proteins interact and cooperate to promote ESC differentiation toward cardiomyocytes.

High-Throughput Toxicity and Phenotypic Screening of 3D Human Neural Progenitor Cell Cultures on a Microarray Chip Platform

Thu, 10/27/2016 - 00:00
Dordick and colleagues demonstrate a 3D cell culture chip for high-throughput screening of immortalized human neural progenitor cells. The dose-response toxicity of 24 compounds was determined on undifferentiated and differentiating hNPCs. Five compounds led to significant differences in IC50 values between undifferentiated and differentiating cultures. This platform has potential use in phenotypic screening to elucidate molecular toxicology on human stem cells.

Small Molecules Modulate Chromatin Accessibility to Promote NEUROG2-Mediated Fibroblast-to-Neuron Reprogramming

Thu, 10/27/2016 - 00:00
In this article, Zhang and colleagues show that NEUROG2 and two small molecules activate transcription and chromatin remodeling programs that drive fibroblast-to-neuron reprogramming in diverse human cell types. Strikingly, the transcription factor SOX4 mediates genome-wide chromatin remodeling processes critical to efficient conversion, while BCL2L1 and the chemical FK228 can improve reprogramming of adult human cell types.

Distinct Enhancer Activity of Oct4 in Naive and Primed Mouse Pluripotency

Thu, 10/27/2016 - 00:00
Do and colleagues show that Oct4 expression is stage-specifically regulated by enhancer activity during embryonic and germ cell development by using a dual reporter system. Enhancer activity is altered in pluripotent stem cells by culture environment, which is regulated by histone modification and DNA methylation.

Marked Differences in C9orf72 Methylation Status and Isoform Expression between C9/ALS Human Embryonic and Induced Pluripotent Stem Cells

Thu, 10/20/2016 - 00:00
Eiges and colleagues characterized two C9/ALS-FTD hESC lines, and compared them with haploidentical and unrelated C9 iPSCs. They show that reprogramming excessively hypermethylates the C9 expansion, and provide evidence that when it is unmethylated the expansion enhances accumulation of repeat-containing mRNAs upon differentiation. Their study supports the potential role of C9 hypermethylation as a neuroprotective mechanism in C9-related ALS.

Rare SOX2+ Airway Progenitor Cells Generate KRT5+ Cells that Repopulate Damaged Alveolar Parenchyma following Influenza Virus Infection

Thu, 10/20/2016 - 00:00
Stripp and colleagues report that H1N1 influenza virus infection in mice induces distal lung epithelial remodeling marked by the appearance of nascent KRT5+ cells in injured airways and alveoli. Rather than pre-existing basal, club, and alveolar progenitor cells, they traced the cellular origin of these nascent KRT5+ cells to a population of airway-resident SOX2+ Lin− progenitor cells.

Transcriptional and Chromatin Dynamics of Muscle Regeneration after Severe Trauma

Thu, 10/20/2016 - 00:00
In this article, Aguilar and colleagues temporally characterize the in vivo dynamics of chromatin modifications and the coding and noncoding transcriptional landscape in a mouse model of traumatic muscle injury to provide a comprehensive view of the central factors that regulate muscle regeneration.

Generation and Analysis of GATA2w/eGFP Human ESCs Reveal ITGB3/CD61 as a Reliable Marker for Defining Hemogenic Endothelial Cells during Hematopoiesis

Thu, 10/13/2016 - 00:00
Pan and colleagues generated GATA2w/eGFP reporter in hESCs, and found that GATA2/eGFP expression defines HECs and HPCs in hESC differentiation. In addition, they showed that CD61 marks HECs and HPCs in hPSC differentiation. Moreover, they revealed that CD61 also marks a small portion of bio-potent HECs in both YS and AGM in E10 mouse embryo.

CNOT3-Dependent mRNA Deadenylation Safeguards the Pluripotent State

Thu, 10/13/2016 - 00:00
In this article, Hu and colleagues showed that CNOT3, a component of the Ccr4-Not deadenylase complex, is required for the maintenance of the pluripotent state in mouse epiblast and embryonic stem cells. They found that CNOT3 promotes differentiation gene mRNA deadenylation and degradation, and post-transcriptionally regulates the gene expression program in pluripotent cells.

Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling

Thu, 10/06/2016 - 00:00
Stein and colleagues investigated whether phenotypic transcription factors have a role in the initial stages of differentiation of human embryonic stem cells before lineage commitment. They discovered selective and transient upregulation of RUNX1 early in mesendodermal differentiation. Multiple experimental approaches provide evidence that RUNX1 regulates EMT and motility through modulation of TGFB2 signaling.

Endogenous DNA Damage Leads to p53-Independent Deficits in Replicative Fitness in Fetal Murine Fancd2−/− Hematopoietic Stem and Progenitor Cells

Thu, 10/06/2016 - 00:00
In this article, Kurre and colleagues demonstrate that FA proteins guard genome integrity during hematopoietic development and balance the inherent stress that coincides with the characteristic rapid fetal cell divisions. FA pathway disruption reveals a unique p53 independent developmental phenotype that constrains proliferative activity and pool expansion without leading to canonical apoptotic attrition seen in experimental models postnatally.

A Dynamic WNT/β-CATENIN Signaling Environment Leads to WNT-Independent and WNT-Dependent Proliferation of Embryonic Intestinal Progenitor Cells

Thu, 10/06/2016 - 00:00
In this article, Spence and colleagues show that WNT/β-CATENIN signaling is dispensable for epithelial progenitor cell proliferation during the pseudostratified stage of intestine development, whereas active signaling is required for proliferation and proper villus formation once villus morphogenesis begins. Mechanistically, WNT/β-CATENIN-mediated proliferation is driven by mesenchymal, but not epithelial, WNT ligand secretion.