Self-Organized Formation of Polarized Cortical Tissues from ESCs and Its Active Manipulation by Extrinsic Signals

SummaryHere, we demonstrate self-organized formation of apico-basally polarized cortical tissues from ESCs using an efficient three-dimensional aggregation culture (SFEBq culture). The generated cortical neurons are functional, transplantable, and capable of forming proper long-range connections in vivo and in vitro. The regional identity of the generated pallial tissues can be selectively controlled (into olfactory bulb, rostral and caudal cortices, hem, and choroid plexus) by secreted patterning factors such as Fgf, Wnt, and BMP. In addition, the in vivo-mimicking birth order of distinct cortical neurons permits the selective generation of particular layer-specific neurons by timed induction of cell-cycle exit. Importantly, cortical tissues generated from mouse and human ESCs form a self-organized structure that includes four distinct zones (ventricular, early and late cortical-plate, and Cajal-Retzius cell zones) along the apico-basal direction. Thus, spatial and temporal aspects of early corticogenesis are recapitulated and can be manipulated in this ESC culture

The role of oxidative stress in the pathogenesis of Alzheimer's disease

[ES]: La presencia de estrés oxidativo es la característica más temprana de la Enfermedad de Alzheimer (EA), lo cual proporciona un atractivo objetivo para intervenciones terapéuticas. Entre los mayores retos que se presentan actualmente están el establecimiento de la fuente de estrés oxidativo y la determinación de cómo este proceso puede influir en la etiología de la Enfermedad de Alzheimer. Este es un tema complejo, pues varios procesos, enzimáticos y no-enzimáticos, están implicados en la formación de oxígeno reactivo y otras moléculas tóxicas. En este artículo discutimos el progreso en el entendimiento de estos procesos[EN]: Oxidative stress is the earliest feature of Alzheimer disease and an attractive therapeutic target. One of the major challenges today is to establish the source of the reactive oxygen and to determine the role of oxidative stress in the etiology of Alzheimer disease. This is a complex issue since a variety of enzymatic and non-enzymatic processes are involved in the formation of reactive oxygen and other toxic molecules. In this review, we discuss progress in the understanding of these processes.Peer reviewe

ガイインセイ シグナル インシ オ フクマナイ バイチ オ モチイタ ハイセイ カンサイボウ カラ フンソク シショウ カブ ソシキ エ ノ ブンカ ユウドウ

京都大学0048新制・課程博士博士(医学)甲第14134号医博第3284号新制||医||971(附属図書館)UT51-2008-N451京都大学大学院医学研究科脳統御医科学系専攻(主査)教授 中辻 憲夫, 教授 篠原 隆司, 教授 長澤 丘司学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Pediatric gliomatosis cerebri presenting with intratumoral hemorrhage leading to poor outcome

Gliomatosis cerebri (GC) is an uncommon disease, defined as diffuse infiltration of neoplastic glial cells involving at least three cerebral lobes. GCs in young population are rare. We described a case of 14-year-old woman with GC who did not receive any recommended treatment, because the patient’s family refused. The patient had a rapid deterioration in 5 months after first symptoms due to intratumoral bleeding. This is the first case report of intratumoral bleeding after diagnosis of GC is made, resulting in poor outcome. GC may acquire possibility of intratumoral hemorrhage through its development

Bone Flap Preservation in Subcutaneous Abdominal Pocket for Decompressive Craniectomy

Summary:. We report our experiences of two pediatric cases in which a bone flap was preserved in the subcutaneous abdominal pocket for decompressive craniectomy. In one case, the bone flap was divided and preserved for cranioplasty without complications; in the other case, the bone flap was left intact as one piece. In pediatric patients, the storage space for a bone flap is sometimes difficult to achieve, and the technique described herein is useful in such situations. Notably, because the bone resorption rate with cryopreservation is higher in pediatric patients, in vivo preservation may be more useful in this population

Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone. Hypothalamic neurons can be generated using a 'self-patterning' strategy that yields a broad array of cell types, or via a more reproducible directed differentiation approach. Stem cell-derived human hypothalamic neurons share characteristic morphological properties and gene expression patterns with their counterparts in vivo, and are able to integrate into the mouse brain. These neurons could form the basis of cellular models, chemical screens or cellular therapies to study and treat common human diseases

Significance of molecular classification of ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are a heterogeneous group of tumors

Abstract Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category