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Updated: 22 hours 26 min ago

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.

Single-Cell Transcriptomic Profiling of Pluripotent Stem Cell-Derived SCGB3A2+ Airway Epithelium

Thu, 04/12/2018 - 00:00
In this article, Kotton and colleagues show that human pluripotent stem cell-derived airway epithelial spheres contain basal and secretory airway cells. Using reporter lines for the secretory airway lineage alongside transcriptomic and functional analyses, they demonstrate that these cells have characteristic features of this population but are susceptible to Wnt-dependent phenotypic drift toward an alveolar type II cell-like program.

Inflammatory Responses and Barrier Function of Endothelial Cells Derived from Human Induced Pluripotent Stem Cells

Thu, 04/12/2018 - 00:00
In this article, Orlova and colleagues show that hiPSC-ECs have similar features to primary ECs but also show some differences. hiPSC-ECs exhibited higher barrier function, lower expression of pro-inflammatory adhesive receptors, and more stringent stromal cell requirements. Importantly, healthy control CD31+ hiPSC-ECs showed high consistency between different batches and lines, forming a good basis for disease modeling applications.

HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition

Tue, 04/10/2018 - 00:00
Thambyrajah et al. established a critical role for HDAC1 and HDAC2 in EHT and identified TGF-β signaling as one of the main pathways modulated by HDAC1 and HDAC2. Activation of TGF-β signaling improves hematopoietic development and would therefore be beneficial for production of hematopoietic cells for regenerative therapies.

Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors

Tue, 04/10/2018 - 00:00
A hallmark of adult neurogenesis is its strong dependence on physiological stimuli and environmental signals. Schulte and colleagues show that the nuclear localization and activity of a transcriptional regulator of adult neurogenesis is controlled by posttranslational modification. Their results link intrinsic control over neuron production to external signals and help to explain how adult neurogenesis can occur “on demand.”

PITX2 Enhances the Regenerative Potential of Dystrophic Skeletal Muscle Stem Cells

Tue, 04/10/2018 - 00:00
Vallejo et al. show that PITX2c enhances the regenerative capability of mouse DYSTROPHIN-deficient satellite cells by increasing cell proliferation and the number of myogenic committed cells but importantly also increasing dystrophin-positive (revertant) myofibers by regulating miR-31.

PLAG1 and USF2 Co-regulate Expression of Musashi-2 in Human Hematopoietic Stem and Progenitor Cells

Tue, 04/10/2018 - 00:00
MSI2 is an essential human hematopoietic stem and progenitor cell (HSPC) regulator, but knowledge of the mechanisms ensuring its appropriate expression in this context are lacking. Here, Hope and colleagues map the MSI2 promoter functional in hematopoietic cells and identify USF2 and PLAG1 as essential, cooperative enforcers of endogenous MSI2 expression and stemness traits in human HSPCs.

Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development

Thu, 04/05/2018 - 00:00
In this report, Storer and colleagues demonstrate that the circulating cytokine IL-6, which is elevated in humans in different pathological situations, can perturb neural stem cell biology after birth. They show that IL-6 signaling is essential for self-renewal and maintenance of post-natal and adult NSCs in the murine forebrain under normal homeostatic conditions.

hPSC-Derived Striatal Cells Generated Using a Scalable 3D Hydrogel Promote Recovery in a Huntington Disease Mouse Model

Thu, 04/05/2018 - 00:00
Adil et al. used a 3D biomaterial to generate hPSC-derived MSN progenitors, which rapidly matured into action potential firing neurons. When striatally transplanted in HD genetic model mice, 3D-generated cells significantly delayed disease onset, alleviated disease symptoms, and increased lifespan. This approach demonstrates the scalable generation of functional MSNs, with implications for clinical translation of cell replacement therapy in HD.

In Vivo Genetic Manipulation of Spermatogonial Stem Cells and Their Microenvironment by Adeno-Associated Viruses

Thu, 04/05/2018 - 00:00
In this article, Shinohara and colleagues show the feasibility of adeno-associated virus (AAV) to penetrate the blood-testis barrier and the basal membrane of the seminiferous tubules of mouse testes. AAVs infected not only germ cells but also their microenvironment. The technique was used to rescue a mouse model of infertility with Sertoli cell defect.

Matched Developmental Timing of Donor Cells with the Host Is Crucial for Chimera Formation

Thu, 03/29/2018 - 00:00
Cohen at al. compares the efficiency of chimera formation in heterochronic and isochronic injections of ESCs and NCCs. Using two distinct and well-characterized pre- and post-implantation chimeric platforms, they show that matching of developmental age of donor cells and the host is essential for chimera formation.

Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia

Thu, 03/29/2018 - 00:00
Brownjohn and colleagues report methods to generate microglia from induced pluripotent human stem cells, which they demonstrate are highly similar to cultured primary human microglia. Microglia differentiated from patient-derived stem cells carrying neurological disease-causing mutations in the TREM2 receptor differentiate normally and respond appropriately to pathogenic stimuli, despite the absence of functional TREM2 receptor on the plasma membrane.

Direct Conversion of Mouse Fibroblasts into Cholangiocyte Progenitor Cells

Thu, 03/29/2018 - 00:00
In this article, Han and colleagues revisited the roles of HepSC-specific factors and found that Hnf1α and Foxa3 facilitate the robust conversion into iHepSCs displaying a relatively closer transcriptional pattern with LEPCs. The prolonged in vitro culture of iHepSCs induces Notch-mediated secondary conversion into iCPCs, which could efficiently be differentiated into mature cholangiocytes.

Heterogeneity of Human Breast Stem and Progenitor Cells as Revealed by Transcriptional Profiling

Thu, 03/29/2018 - 00:00
In this article, Colacino and colleagues use flow-cytometry-sorted populations and single-cell analyses to investigate human mammary stem cells. They discover unexpected phenotypic and functional heterogeneity at the single-cell level, including a subpopulation of ALDH+ stem cells with a hybrid epithelial/mesenchymal phenotype and triple-negative breast cancer-like gene expression pattern.

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