Data describing Rax positive optic-vesicle generation from mouse embryonic stem cells in vitro

AbstractThis article contains data related to the research article entitled “Specification of embryonic stem cell-derived tissues into eye fields by Wnt signaling using rostral diencephalic tissue-inducing culture” Sakakura (2016) [1]. Mouse embryonic stem cells (ESC) were used for the generation of optic vesicle-like tissues in vitro. In this article we described data in which a Rax::GFP knock-in ESC line was used to monitor the formation of optic tissues. In addition, we also described the data of regional marker expression of Rax, Sox2 and Pax6 in vivo around the forebrain and the eye tissues for comparative purposes. These data can be valuable to researchers interested in investigating forebrain and eye tissue development

Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells

Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms in vitro following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the in vitro-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine

リポジトリ用データ管理システムの構築

金沢大学総合メディア基盤センター近年のオープンサイエンスの活発化に伴い, 人間と機械の双方に可読性を持つリポジトリシステムの需要が高まっている. このような背景から, 本研究では, 国立情報学研究所が開発したWEKO を用いて, 金沢大学環日本海域環境研究センター及び同国際文化資源学研究センターのデータリポジトリの構築を行っている.従来, WEKO へのコンテンツの一括登録には, Windows でのみ動作するソフトウェアが必要であった. 我々は, ICT に精通しているとは限らないデータ所有者が, リポジトリ上のデータ管理を行えるように, OS に非依存なブラウザからファイルをアップロードするだけでコンテンツの一括登録に加え, メタデータやコンテンツの追加登録・更新等が可能なデータ管理システムを構築した. 特に更新機能では, 「更新フラグ」属性を用いて, コンテンツの世代管理とその公開方法の制御を可能にした. 本稿では両センターのデータリポジトリと構築したデータ管理システムの概要を述べる.Along with the recent activation of open science, the demand for a repository system that is readable to both humans and machines is increasing. In this context, we constructed data repositories for Institute of Nature and Environmental Technology and Center for Cultural Resource Studies in Kanazawa University using WEKO, which is a repository platform developed by the National Institute of Informatics. In the original design of the WEKO, it is necessary to utilize software for Windows for batch registration of data contents. In the present study, we developed a new user interface for data management for data owners who are not familiar with ICT. By using this system, it is possible for data owners to operate a batch processing for additional registration, update of the registered contents and modication of the metadata simply by uploading a le via browser without depending on the OS. Particularly, it is innovative that out software supports revision control and data access control of the contents by setting "update ag"attribute. In this paper, we introduce the user interface developed for the data repositories in Kanazawa University

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target