Tissue- and Cell-Type-Specific Manifestations of Heteroplasmic mtDNA 3243A>G Mutation in Human Induced Pluripotent Stem Cell-Derived Disease Model The authors produced induced pluripotent stem cells (iPSCs) from patients carrying the most common mitochondrial DNA (mtDNA) mutation, m.3243A>G. During reprogramming, the cells underwent an mtDNA bottleneck, mimicking that in epiblast specification. They differentiated iPSCs to heteroplasmic human cells and tissues with isogenic nuclear background and show that the disease manifestation depends on cellular context. [Proc Natl Acad Sci USA] Abstract Reduced Ciliary Polycystin-2 in Induced Pluripotent Stem Cells from Polycystic Kidney Disease Patients with PKD1 Mutations Heterozygous mutations in PKD1 or PKD2, which encode polycystin-1 and polycystin-2, respectively, cause autosomal dominant PKD (ADPKD), whereas mutations in PKHD1, which encodes fibrocystin/polyductin, cause autosomal recessive PKD (ARPKD). However, the relationship between these proteins and the pathogenesis of PKD remains unclear. To model PKD in human cells, investigators established induced pluripotent stem cell lines from fibroblasts of three ADPKD and two ARPKD patients. [J Am Soc Nephrol] Abstract | Press Release Directed Differentiation and Neurite Extension of Mouse Embryonic Stem Cell on Aligned Poly(Lactide) Nanofibers Functionalized with YIGSR Peptide Fibers that were both aligned and functionalized with Tyr-Ile-Gly-Ser-Arg (YIGSR) were found to significantly increase the fraction of mouse embryonic stem cells (mESC) expressing neuron-specific class III beta-tubulin, the level of neurite extension and gene expression for neural markers compared to mESC cultured on random fiber mats and unfunctionalized matrices. [Biomaterials] Abstract BMP4-Directed Trophoblast Differentiation of Human Embryonic Stem Cells Is Mediated through a ΔNp63+ Cytotrophoblast Stem Cell State Scientists showed that BMP4-treated human embryonic stem cells differentiate into bona fide cytotrophoblasts (CTB) by direct comparison with primary human placental tissues and isolated CTB through gene expression profiling. [Development] Abstract Derivation of Embryonic Stem Cell Lines from Parthenogenetically Developing Rat Blastocysts The authors attempted to establish rat embryonic stem (ES) cells from parthenogenetically developing blastocysts. Ten blastocysts were prepared by treatment of ovulated rat oocytes with ionomycin and cycloheximide, and three alkaline phosphatase-positive ES cell lines were established using N2B27 medium supplemented with mitogen activated protein kinase kinase inhibitor PD0325901, glycogen synthase kinase 3 inhibitor CHIR99021, rat leukemia inhibitory factor, and forskolin. [Stem Cell Dev] Abstract Morphological Differences of Primary Cilia between Human Induced Pluripotent Stem Cells and Their Parental Somatic Cells Researchers found high expression of hedgehog signaling proteins Patched1 (Ptch1), Smoothened (Smo), Gli1, and Gli2 in reprogrammed cells. Stimulation of the hedgehog pathway resulted in the concerted movement of Ptch1 out of the cilia and Smo into the cilia, implying that the cilia on induced pluripotent stem cells contain functioning hedgehog machinery. [Stem Cell Dev] Abstract Minimally Invasive Transplantation of iPSC-Derived ALDHhiSSCloVLA4+ Neural Stem Cells Effectively Improves the Phenotype of an Amyotrophic Lateral Sclerosis Model The authors isolated a specific neural stem cell (NSC) population from human induced pluripotent stem cells (iPSCs) based on high aldehyde dehydrogenase activity, low side scatter, and integrin VLA4 positivity. They assessed the therapeutic effects of these NSCs on the phenotype of amyotrophic lateral sclerosis mice after intrathecal or intravenous injections. [Hum Mol Genet] Abstract Functional Recovery after Transplantation of Induced Pluripotent Stem Cells in a Rat Hemorrhagic Stroke Model Researchers investigated the functional outcome of induced pluripotent stem cells (iPSCs) transplantation in experimental intracerebral hemorrhage (ICH) in rats. IPSCs were derived from an ICH patient’s fibroblasts and were injected into the ipsilateral side of ICH in rats. [Neurosci Lett] Abstract Mammalian Genes Induce Partially Reprogrammed Pluripotent Stem Cells in Non-Mammalian Vertebrate and Invertebrate Species Scientists found that a set of four mammalian transcription factor genes used to generate induced pluripotent stem cells in mouse and humans can induce a partially reprogrammed pluripotent stem cell state in vertebrate and invertebrate model organisms, in mammals, birds, fish, and fly, which span 550 million years from a common ancestor. [eLife] Full Article |