Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons
Bhaskar Chanda Stem Cell Jo et al. report a method for generating human midbrain-like organoids (hMLOs) from hPSCs in 3D culture. The hMLOs contain distinct layers of neuronal cells expressing human midbrain markers, such as neuromelanin, are electrically active, form functional synapses, and produce dopamine, suggesting that they may be useful for studying human midbrain.
Bhaskar Chanda Stem Cell Rinaldi et al. show that Dnmt3a and Dnmt3b associate to and activate enhancers. Whereas Dnmt3a induces enhancer DNA hydroxymethylation, Dnmt3b promotes enhancer DNA methylation. Both proteins regulate epidermal SC homeostasis.
Epigenetic Variation between Human Induced Pluripotent Stem Cell Lines Is an Indicator of Differentiation Capacity
Bhaskar Chanda Stem Cell Nishizawa et al. integrate analysis of differentiation outcome and molecular characterization to identify features of human iPSCs associated with high and low capacities for hematopoietic specification and maturation. Prospective use of this type of information could help in choosing iPSC lines best suited to different applications.
Bhaskar Chanda Stem Cell Przybyla et al. describe how properties of the extracellular matrix can direct fate specification in hESCs. They show that mechanical forces resulting from differential matrix stiffness translate via junctional organization, Src, and β-catenin into transcriptional responses that drive mesodermal differentiation.
Bhaskar Chanda Stem Cell Several studies have suggested that some iPSC clones display tumorigenic and immunogenic potential as well as variations in their differentiation potential, thus raising concerns about their utility and safety in the clinical setting. Tapia and Schöler discuss these molecular obstacles and how they may affect clinical translation of iPSC technology.
Conversion of Human Gastric Epithelial Cells to Multipotent Endodermal Progenitors using Defined Small Molecules
Bhaskar Chanda Stem Cell Wang et al. show that a set of defined small molecules plus mesenchymal feeder cells can covert human gastric epithelial cells into induced endodermal progenitors with multilineage differentiation capacity. As gastric epithelial cells are readily available after surgical/biopsy procedures, these cells could provide an accessible source for various applications.
Bhaskar Chanda Stem Cell Theunissen et al. use molecular criteria based on transposon expression, DNA methylation, and X chromosome status to compare naive human pluripotent cells to human preimplantation embryos. Current approaches yield cells that most closely resemble the morula/early blastocyst stage.
Ectopic miR-125a Expression Induces Long-Term Repopulating Stem Cell Capacity in Mouse and Human Hematopoietic Progenitors
Bhaskar Chanda Stem Cell Wojtowicz et al. report that enforced expression of miR-125a confers enhanced long-term self-renewal potential to multipotent hematopoietic progenitors (MPPs). Quantitative proteomics reveals a miR-125a target network that normally functions to restrain self-renewal in more committed progenitors. These results suggest that enhanced MPPs may be used to augment limited HSC sources.
The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling
Bhaskar Chanda Stem Cell In this study, North and colleagues uncover serotonin-stimulated central regulation of hematopoietic stem cell production during embryonic development, mediated by the stress-responsive hypothalamic-pituitary-adrenal/interrenal (HPA/I) axis and glucocorticoid receptor. Significantly, the hypoxic stress sensor Hif1α is a physiologic initiator of CNS-derived serotonin synthesis and central feedback regulation of embryonic HSC numbers.