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Updated: 39 min 12 sec ago

Large-Scale Expansion of Human iPSC-Derived Skeletal Muscle Cells for Disease Modeling and Cell-Based Therapeutic Strategies

Thu, 05/03/2018 - 00:00
Van der Wal et al. present a robust protocol for the transgene-free generation and purification of myogenic progenitors from human iPSCs and for their expansion up to 5 × 1011-fold. After gene editing in vitro, these myogenic progenitors matured into contractile skeletal muscle cells, reversing Pompe disease pathology. In vivo, myogenic progenitors contributed to muscle regeneration.

INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice

Thu, 04/26/2018 - 00:00
Palacio et al. find that ionizing radiation induces the senescence marker INK4a/ARF in neural progenitor cells and demonstrate that such expression as a mechanism leading to loss of neurogenesis. Their results suggest that treatments looking to preserve stem cell regenerative potential, by limiting INK4a/ARF expression, may help prevent radiation-related loss of neurogenesis.

Inducible Expression of GDNF in Transplanted iPSC-Derived Neural Progenitor Cells

Thu, 04/26/2018 - 00:00
Svendsen, Breunig, and colleagues generated a plasmid containing a tetracycline transactivator and a response element expressing dual reporters and GDNF. Stably transduced human iPSC-derived neural progenitors show inducible, reversible expression of GDNF, a fluorescent reporter protein, and luciferase in vitro and following transplantation into the mouse brain. This combined cell and gene therapy advancement is promising for neurodegenerative diseases.

Unraveling the Inconsistencies of Cardiac Differentiation Efficiency Induced by the GSK3β Inhibitor CHIR99021 in Human Pluripotent Stem Cells

Thu, 04/26/2018 - 00:00
In this article, Laco and colleagues show that human pluripotent stem cells are characterized by individual cell-cycle profiles. Changes in cell-cycle profiles, mainly due to cell culture density, affect Wnt pathway-induced cardiac differentiation and cell death when GSK3β inhibitors are applied. We show that cell-cycle validation is crucial for stem cell quality and experimental reproducibility.

The STAT3 Target Mettl8 Regulates Mouse ESC Differentiation via Inhibiting the JNK Pathway

Thu, 04/26/2018 - 00:00
In this article, Fu and colleagues show that STAT3 positively regulates gene expression of Mettl8 in mouse ESCs. METTL8 is dispensable for pluripotency but affects ESC differentiation by interacting with Mapkbp1 mRNA and inhibiting its translation. MAPKBP1 mediates the effect of METTL8 to JNK signaling during mouse ESC differentiation.

Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration

Thu, 04/26/2018 - 00:00
In this article, Mayerl and colleagues demonstrate that the thyroid hormone transporters MCT8 and OATP1C1 are unique gate-keepers in activated muscle stem cells. The expression of both transporters increases upon activation of muscle stem cells, while loss of MCT8 and OATP1C1 expression results in impaired muscle stem cell differentiation.

Dissecting the Contributions of Cooperating Gene Mutations to Cancer Phenotypes and Drug Responses with Patient-Derived iPSCs

Thu, 04/19/2018 - 00:00
Papapetrou and colleagues develop a comprehensive panel of isogenic iPSC lines with SRSF2 P95L mutation and chr7q deletion. They use these cells to identify cellular phenotypes contributed by each genetic lesion and therapeutic vulnerabilities specific to each one and develop expandable hematopoietic progenitor cell lines to facilitate drug discovery.

X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs

Thu, 04/19/2018 - 00:00
Somatic cells can be reprogrammed to iPSCs, inducing reactivation of the inactive X chromosome. Using genome-scale DNA methylation analyses, Plath, Pasque, and colleagues show that iPSCs adopt sex-specific differences in global DNA methylation that correlate with the presence of two active X chromosomes. Upon culture, female iPSCs lose one of the two X chromosomes and adopt male-like DNA methylation.

DNA Methylation and Regulatory Elements during Chicken Germline Stem Cell Differentiation

Thu, 04/19/2018 - 00:00
In this article, Song, Li, and their colleagues reported a comprehensive genome-wide DNA methylation landscape in chicken germ cells. The integrated epigenetic mechanisms were explored, specifically, germ cell differentiation experiences through a highly orchestrated process that involves multiple epigenetic events, which would give a clue for curing male infertility in animals and humans.

Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture

Thu, 04/19/2018 - 00:00
In this article, U. Martin and colleagues show the generation of hiPSC endothelial cells in scalable cultures in up to 100 mL culture volume. The generated ECs show in vitro proliferation capacity and a high degree of chromosomal stability after in vitro expansion. The established protocol allows to generate hiPSC-derived ECs in relevant numbers for regenerative approaches.

FGF2 Has Distinct Molecular Functions from GDNF in the Mouse Germline Niche

Thu, 04/19/2018 - 00:00
Takashima and colleagues demonstrate the novel functions of FGF2 in the germline niche. Although FGF2 induces self-renewal of spermatogonial stem cells in vitro, this molecule expands “differentiation-prone” GFRA1+RARG+ spermatogonia and facilitates retinoic acid actions required for differentiation in vivo. The present study suggests that FGF2 contributes to spermatogonial differentiation, indicating reconsideration of the role of FGF2 in the germline niche.

NF-κB Activity Initiates Human ESC-Derived Neural Progenitor Cell Differentiation by Inducing a Metabolic Maturation Program

Thu, 04/19/2018 - 00:00
In this research article, FitzPatrick and colleagues have highlighted the requirement for NF-κB signaling in neural specification of human embryonic stem cells. They demonstrate that its activity orchestrates a metabolic shift toward oxidative phosphorylation in committing neural progenitor cells. Moreover, they demonstrate that progenitor cells with increased endogenous NF-κB activity have a higher propensity for maturation.

The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific Regulation

Thu, 04/19/2018 - 00:00
Engström and colleagues show that Drosophila Nubbin, a homolog of mammalian OCT1 and OCT4, controls stem cell proliferation and differentiation in the fly midgut. Two isoforms, Nub-PB and Nub-PD, regulate progenitor cell fate antagonistically, as loss of Nub-PB provokes hyperplasia, while loss of Nub-PD blocks stem cell proliferation. In addition, Nub-PB acts as a differentiation factor and strong tumor suppressor.

Dissecting the Contributions of Cooperating Gene Mutations to Cancer Phenotypes and Drug Responses with Patient-Derived iPSCs

Thu, 04/19/2018 - 00:00
Papapetrou and colleagues develop a comprehensive panel of isogenic iPSC lines with SRSF2 P95L mutation and chr7q deletion. They use these cells to identify cellular phenotypes contributed by each genetic lesion and therapeutic vulnerabilities specific to each one and develop expandable hematopoietic progenitor cell lines to facilitate drug discovery.

X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs

Thu, 04/19/2018 - 00:00
Somatic cells can be reprogrammed to iPSCs, inducing reactivation of the inactive X chromosome. Using genome-scale DNA methylation analyses, Plath, Pasque, and colleagues show that iPSCs adopt sex-specific differences in global DNA methylation that correlate with the presence of two active X chromosomes. Upon culture, female iPSCs lose one of the two X chromosomes and adopt male-like DNA methylation.

DNA Methylation and Regulatory Elements during Chicken Germline Stem Cell Differentiation

Thu, 04/19/2018 - 00:00
In this article, Song, Li, and their colleagues reported a comprehensive genome-wide DNA methylation landscape in chicken germ cells. The integrated epigenetic mechanisms were explored, specifically, germ cell differentiation experiences through a highly orchestrated process that involves multiple epigenetic events, which would give a clue for curing male infertility in animals and humans.

Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture

Thu, 04/19/2018 - 00:00
In this article, U. Martin and colleagues show the generation of hiPSC endothelial cells in scalable cultures in up to 100 mL culture volume. The generated ECs show in vitro proliferation capacity and a high degree of chromosomal stability after in vitro expansion. The established protocol allows to generate hiPSC-derived ECs in relevant numbers for regenerative approaches.

FGF2 Has Distinct Molecular Functions from GDNF in the Mouse Germline Niche

Thu, 04/19/2018 - 00:00
Takashima and colleagues demonstrate the novel functions of FGF2 in the germline niche. Although FGF2 induces self-renewal of spermatogonial stem cells in vitro, this molecule expands “differentiation-prone” GFRA1+RARG+ spermatogonia and facilitates retinoic acid actions required for differentiation in vivo. The present study suggests that FGF2 contributes to spermatogonial differentiation, indicating reconsideration of the role of FGF2 in the germline niche.

NF-κB Activity Initiates Human ESC-Derived Neural Progenitor Cell Differentiation by Inducing a Metabolic Maturation Program

Thu, 04/19/2018 - 00:00
In this research article, FitzPatrick and colleagues have highlighted the requirement for NF-κB signaling in neural specification of human embryonic stem cells. They demonstrate that its activity orchestrates a metabolic shift toward oxidative phosphorylation in committing neural progenitor cells. Moreover, they demonstrate that progenitor cells with increased endogenous NF-κB activity have a higher propensity for maturation.

The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific Regulation

Thu, 04/19/2018 - 00:00
Engström and colleagues show that Drosophila Nubbin, a homolog of mammalian OCT1 and OCT4, controls stem cell proliferation and differentiation in the fly midgut. Two isoforms, Nub-PB and Nub-PD, regulate progenitor cell fate antagonistically, as loss of Nub-PB provokes hyperplasia, while loss of Nub-PD blocks stem cell proliferation. In addition, Nub-PB acts as a differentiation factor and strong tumor suppressor.

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