Functional Genomic Screen of Human Stem Cell Differentiation Reveals Pathways Involved in Neurodevelopment and Neurodegeneration Human embryonic stem cells can be induced and differentiated to form a relatively homogeneous population of neuronal precursors in vitro. Investigators used this system to screen for genes necessary for neural lineage development by using a pooled human short hairpin RNA library screen and massively parallel sequencing. [Proc Natl Acad Sci USA] Abstract Modeling Key Pathological Features of Frontotemporal Dementia with C9ORF72 Repeat Expansion in iPSC-Derived Human Neurons Researchers generated a human neuronal model and investigated the pathological phenotypes of human neurons containing GGGGCC repeat expansions. Skin biopsies were obtained from two subjects who had >1,000 GGGGCC repeats in C9ORF72 and their respective fibroblasts were used to generate multiple induced pluripotent stem cell (iPSC) lines. [Acta Neuropathol] Full Article Insulin and IGFs Enhance Hepatocyte Differentiation from Human Embryonic Stem Cells via the PI3K/AKT Pathway Scientists found that insulin enhanced hepatocyte differentiation from human embryonic stem cell-derived definitive endoderm (DE). Insulin activated the PI3K/AKT pathway, but not the MAPK pathway in the DE cells, and inhibition of the PI3K/AKT pathways by inhibitors markedly inhibited hepatocyte differentiation. In addition, IGF1 and IGF2 also activated the PI3K/AKT pathway in DE cells and their expression was robustly upregulated during hepatocyte differentiation from DE. [Stem Cells] Abstract A Microparticle Approach to Morphogen Delivery within Pluripotent Stem Cell Aggregates Researchers describe a microparticle (MP)-based approach to deliver growth factors within multicellular aggregates to direct pluripotent stem cell differentiation. Compared to conventional soluble delivery methods, gelatin MPs laden with bone morphogenic protein-4 or noggin induced efficient gene expression of mesoderm and ectoderm lineages, respectively, despite using nearly 12-fold less total growth factor. [Biomaterials] Abstract | Press Release Induction of Inner Ear Hair Cell-Like Cells from Math1-Transfected Mouse ES Cells Although embryonic stem (ES) cells are able to produce hair cell (HC)-like cells, the role of Math1 in induction of those cells has not been thoroughly elucidated. The authors introduced Math1 into ES cells in order to achieve efficient generation of HC-like cells. [Cell Death Dis] Full Article Influence of Activin A Supplementation during Human Embryonic Stem Cell Derivation on Germ Cell Differentiation Potential Human embryonic stem cells (hESCs) are more similar to ‘primed’ mouse epiblast stem cells (mEpiSCs). mEpiSCs, which are derived in Activin A, show an increased propensity to form primordial germ cell (PGC)-like cells in response to bone morphogenic protein 4 (BMP4). Hence, the authors hypothesized that hESCs derived in the presence of Activin A may be more competent in differentiating towards PGC-like cells after supplementation with BMP4 compared to standard hESC lines. [Stem Cells Dev] Abstract TPC2 Signaling Inhibits Autophagosomal-Lysosomal Fusion by Alkalizing Lysosomal pH Scientists found that overexpression of two pore channel 2 (TPC2) in HeLa or mouse embryonic stem (ES) cells inhibited autophagosomal-lysosomal fusion, thereby resulting in the accumulation of autophagosomes. Treatment of TPC2 expressing cells with a cell permeant-NAADP agonist, NAADP-AM, further induced autophagosome accumulation. On the other hand, TPC2 knockdown or treatment of cells with Ned-19, a NAADP antagonist, markedly decreased the accumulation of autophagosomes. [J Biol Chem] Abstract | Full Article Overexpression of miR-122 Promotes the Hepatic Differentiation and Maturation of Mouse ESCs through a miR-122/FoxA1/HNF4a-Positive Feedback Loop Researchers aimed to elucidate the effect and underlying mechanisms of microRNA (miR)-122 during differentiation of embryonic stem cells (ESCs) into hepatocytes. [Liver Int] Abstract |