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The reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) raises the possibility that a somatic cell could be reprogrammed to an alternative differentiated fate without first becoming a stem/progenitor cell. A large pool of fibroblasts exists in the postnatal heart, yet no single "master regulator" of direct cardiac reprogramming has been(More)
Direct reprogramming of adult somatic cells into alternative cell types has been shown for several lineages. We previously showed that GATA4, MEF2C, and TBX5 (GMT) directly reprogrammed nonmyocyte mouse heart cells into induced cardiomyocyte-like cells (iCMs) in vitro and in vivo. However, GMT alone appears insufficient in human fibroblasts, at least in(More)
Uterine transplantation experiments have been performed in various animal species for future clinical applications of uterine transplantation for permanent uterine factor infertility in humans. The aim of this study was to confirm the feasibility of uterine auto-transplantation in cynomolgus monkeys by developing new surgical techniques. Two female(More)
Various peripheral tissues show circadian rhythmicity, which is generated at the cellular level by their own core oscillators that are composed of transcriptional/translational feedback loops involving a set of clock genes. Although the circulating levels of some adipocytokines, i.e. bioactive substances secreted by adipocytes, are on a 24-h rhythmic cycle,(More)
Reprogramming differentiated cells into induced pluripotent stem cells (iPSCs) promotes a broad array of cellular changes. Here we show that the let-7 family of microRNAs acts as an inhibitory influence on the reprogramming process through a regulatory pathway involving prodifferentiation factors, including EGR1. Inhibiting let-7 in human cells promotes(More)
Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that replicates and transcribes in the nucleus of infected cells. Therefore, efficient synthesis of BDV RNA in the nucleus is critical for the development of a reverse genetics system for this virus. Here, we report the development of such a system using the RNA polymerase II (Pol II)(More)
Extracellular matrix (ECM) components regulate stem-cell behavior, although the exact effects elicited in embryonic stem (ES) cells are poorly understood. We previously developed a simple, defined, serum-free culture medium that contains leukemia inhibitory factor (LIF) for propagating pluripotent mouse embryonic stem (mES) cells in the absence of feeder(More)
Recent studies have shown the gene expression of several transporters to be circadian rhythmic. However, it remains to be elucidated whether the expression of P-glycoprotein, which is involved in the transport of many medications, undergoes 24 h rhythmicity. To address this issue, we investigated daily profiles of P-glycoprotein mRNA and protein levels in(More)
Infertility caused by the disruption or absence of germ cells (i.e., sperm or egg) is a major and largely incurable medical problem. In vitro disease modeling using normal human germline cells is required to better understand the precise molecular mechanisms of infertility and to develop drugs to treat this condition. Recent advances in the differentiation(More)
Enzymes used for passaging human pluripotent stem cells (hPSCs) digest cell surface proteins, resulting in cell damage. Moreover, cell dissociation using divalent cation-free solutions causes apoptosis. Here we report that Mg(2+) and Ca(2+) control cell-fibronectin and cell-cell binding of hPSCs, respectively, under feeder- and serum-free culture conditions(More)