Mutation of the histone demethylase Gasc1 causes ASD-like symptoms in mice.

Background: Genomic analyses of psychiatric disorders, including autism spectrum disorder (ASD), have revealed many susceptibility genes, suggesting that such disorders may be caused by multiple factors. In this sense, it has long been a question whether there is an abnormal genetic status that comprehensively explains the pathogenesis of neuropsychiatric disorders or a"promising upstream treatment target"that normalizes symptoms.

Methods: To address this question, we provide important clues with respect to GASC1 (JMJD2 C/KDM4 C), which is a histone demethylase that prominently targets trimethylated histone H3 at lysine 9 (H3 K9 me3).

Transient ETV2 Expression Promotes the Generation of Mature Endothelial Cells from Human Pluripotent Stem Cells.

Differentiation protocols are used for induced pluripotent stem cells (iPSCs) in in vitro disease modeling and clinical applications. Transplantation of endothelial cells (ECs) is an important treatment strategy for ischemic diseases. For example, in vitro generated ECs can be used to provide the vascular plexus to regenerate organs such as the liver.

Effect of heat stress on blood-brain barrier integrity in iPS cell-derived microvascular endothelial cell models.

The incidence of heatstroke has been increasing. Heatstroke has been shown to affect physiological barrier functions. However, there are few studies of the effect of heat stress on the blood-brain barrier (BBB) function.

In vitro model of cerebral ischemia by using brain microvascular endothelial cells derived from human induced pluripotent stem cells.

Brain-derived microvascular endothelial cells (BMECs), which play a central role in blood brain barrier (BBB), can be used for the evaluation of drug transport into the brain. Although human BMEC cell lines have already been reported, they lack original properties such as barrier integrity. Pluripotent stem cells (PSCs) can be used for various applications such as regenerative therapy, drug screening, and pathological study.

Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by iron chelation.

Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection.

A Synthetic Polymer Scaffold Reveals the Self-Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche.

Cancer stem cells (CSCs) are believed to be maintained within a microenvironmental niche. Here we used polymer microarrays for the rapid and efficient identification of glioma CSC (GSC) niche mimicries and identified a urethane-based synthetic polymer, upon which two groups of niche components, namely extracellular matrices (ECMs) and iron are revealed. In cultures, side population (SP) cells, defined as GSCs in the rat C6 glioma cell line, are more efficiently sustained in the presence of their differentiated progenies expressing higher levels of ECMs and transferrin, while in xenografts, ECMs are supplied by the vascular endothelial cells (VECs), including SP cell-derived ones with distinctively greater ability to retain xenobiotics than host VECs.

Induction of protumoral CD11c(high) macrophages by glioma cancer stem cells through GM-CSF.

Cancer stem cells (CSCs) are maintained under special microenvironment called niche, and elucidation and targeting of the CSC niche will be a feasible strategy for cancer eradication. Tumor-associated macrophages (TAMs) are known to be involved in cancer progression and thus can be a component of CSC niche. Although TAMs are known to play multiple roles in tumor progression, involvement of CSCs in TAM development fully remains to be elucidated.

Increase in GFAP-positive astrocytes in histone demethylase GASC1/KDM4C/JMJD2C hypomorphic mutant mice.

GASC1, also known as KDM4C/JMJD2C, is a histone demethylase for histone H3 lysine 9 (H3K9) and H3K36. In this study, we observed an increase of GFAP-positive astrocytes in the brain of Gasc1 hypomorphic mutant mice at 2-3 months of age, but not at postnatal day 14 and day 30 by immunohistochemistry. Increases of GFAP-positive astrocytes were widely observed in the forebrain and prominent in such regions as cerebral cortex, caudate putamen, amygdala and diencephalon, but not obvious in hippocampus.