{"id":"hum0130","version":1,"url":"https://humandbs.dbcls.jp/research/hum0130/v1","datePublished":"2019-01-18","versions":[{"version":1,"datePublished":"2019-01-18"},{"version":2,"datePublished":"2022-09-27"},{"version":3,"datePublished":"2024-06-17"}],"title":{"ja":"POEMS症候群の骨髄細胞における遺伝子異常の網羅的解析 / 造血器腫瘍と骨髄ニッチ細胞の遺伝子異常解析による分子病態の解明と新規治療薬開発の基盤構築","en":"Comprehensive genetic analyses of bone marrow cells in POEMS syndrome / Analyses of molecular mechanisms of hematological malignancies and bone marrow niche"},"summary":{"aims":{"ja":"POEMS症候群（polyneuropathy, organomegaly, endocrinopathy, M-Protein, and skin changes syndrome）における形質細胞の遺伝学的特徴を他の形質細胞性疾患と比較する。POEMS症候群患者の骨髄形質細胞におけるWhole Exome Sequencing, 標的シークエンス、bulk RNAシークエンス、更にシングルセルRNAシークエンスを行い、POEMSクローンの遺伝子発現の特徴を明らかにすることで、本疾患の分子病態解明を行う。","en":"To compare genetic features of plasma cells from polyneuropathy, organomegaly, endocrinopathy, M-Protein, and skin changes (POEMS) syndrome, multiple myeloma (MM), and monoclonal gammopathy of undetermined significance (MGUS), we herein performed WES, target sequencing, bulk RNA-seq, single-cell RNA Seq of bone marrow (BM) plasma cells from patients with POEMS syndrome and compared them with other diseases and normal controls. These data unveil unique features of POEMS clones among plasma cell neoplasms and enhance our understanding of the pathogenesis of POEMS syndrome."},"methods":{"ja":"POEMS症候群における形質細胞のゲノム解析および3疾患（POEMS症候群、多発性骨髄腫、単クローン性免疫グロブリン血症 [monoclonal gammopathy of undetermined significance：MGUS]）の遺伝子発現解析。患者骨髄からCD138陽性形質細胞をMACSとFACSによって純化し、Fluidigm C1を用いてシングルセルソートとライブラリー作成を行い、Illumina HiSeq 3000にてRNAシークエンスを行った。また、SMART-Seq v4 Ultra Low Input RNA Kit for Sequencing、NEBNext Ultra DNALibrary Prep Kitを用いてライブラリーを作成し、Illumina HiSeq 2000にてRNAシークエンスを行った。骨髄腫浸潤のない早期リンパ腫3症例の骨髄形質細胞からCD138陽性形質細胞をMACSとFACSによって純化し、抽出したRNAを用いたRNAシークエンスを行った。","en":"Genomic analysis of POEMS syndrome, and gene expression analysis of 3 diseases. For scRNA-Seq, CD138+ plasma cells were purified by FACS after MACS CD138 positive selection from BM aspiration samples. Single cell isolation and library preparation were performed by Fluidigm C1, and then the samples were read by single-end sequencing with Illumina HiSeq 3000. For bulk RNA-Seq, library preparation was performed by SMART-Seq v4 Ultra Low Input RNA Kit for Sequencing and NEBNext Ultra DNA Library Prep Kit. Then the samples were read by paired-end sequencing with Illumina HiSeq 2000. RAN-seq was performed on bone marrow plasma cells purified by fluorescence-activated cell sorting (FACS) after CD138-positive magnetic cell separation. RNA samples were obtained from 3 early-stage lymphoma patients without BM invasion as normal controls."},"targets":{"ja":"POEMS症候群、多発性骨髄腫、MGUS、正常コントロール（骨髄浸潤のない悪性リンパ腫）の形質細胞。症例数は個別に記載。","en":"Plasma cells from POEMS syndrome, MM, MGUS, and Normal control (lymphoma without BM invasion)"},"url":{"ja":null,"en":null}},"listingSummary":{},"releaseNote":{"ja":"POEMS症候群20症例、多発性骨髄腫4例、MGUS5例の骨髄液から単離した形質細胞から抽出したDNAおよびRNAを使用したExome解析データ（bam）、Target Capture解析データ（bam）、および、RNA-seq解析データ（fastq）を提供する。","en":"DNAs and RNAs extracted from plasma cells of 20 POEMS syndrome, 4 MM and 5 MGUS patients were used for the whole exome sequencing analysis (bam files), target capture seqencing analysis (bam files), and RNA sequencing analysis (fastq files)."},"dataProviders":[{"name":{"ja":"堺田 恵美子","en":"Emiko Sakaida"},"organization":{"name":{"ja":"千葉大学大学院医学研究院・細胞治療内科学（千葉大学病院 血液内科）","en":"Chiba University Graduate school of Medicine, Clinical Cell Bilogy and Medicine"}}}],"researchProjects":[],"grants":[{"title":{"ja":"骨髄微少環境と形質細胞の相互作用に基づいたPOEMS症候群の発症機構の解明","en":"Genetic and transcriptional landscape of plasma cells in POEMS syndrome"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["26461397"]},{"title":{"ja":"次世代シークエンサーによるMRD検出法に基づくPOEMS症候群の治療戦略の確立","en":"Clonal immunoglobulin lamda light-chain gene rearrangements detected by NGS in POEMS syndrome"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["15K09494"]},{"title":{"ja":"骨髄形質細胞シングルセル解析によるPOEMS症候群の分子病態の解明","en":"Elucidation of the molecular mechanism of POEMS syndrome by single cell analysis of bone marrow plasma cells"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["18K08338"]},{"title":{"ja":"先進ゲノム解析研究推進プラットフォーム","en":"Platform for Advanced Genome Science"},"agency":{"ja":"科学研究費助成事業 新学術領域研究（研究領域提案型）『学術研究支援基盤形成』","en":"KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas - Platforms for Advanced Technologies and Research Resources"},"grantIds":["16H06279"]},{"title":{"ja":"造血幹細胞エイジングを規定するエピジェネティック機構の統合的理解","en":"Deciphering of the epigenetic machinery that determines the hallmarks of hematopoietic stem cell aging"},"agency":{"ja":"科学研究費助成事業 基盤研究（S）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["19H05653"]},{"title":{"ja":"幹細胞の運命決定に関わるクロマチン複製機構の解明","en":"Characterization of chromatin replication associated with stem cell fate decision"},"agency":{"ja":"科学研究費助成事業 新学術領域研究（研究領域提案型）","en":"KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)"},"grantIds":["19H05746"]},{"title":{"ja":"POEMS症候群における微小クローン同定による診断治療戦略の確立","en":"Establishment of diagnostic and therapeutic strategies by identification of small clones in POEMS syndrome"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (S)"},"grantIds":["22K08471"]}],"relatedPublications":[{"title":"Genetic and transcriptional landscape of plasma cells in POEMS syndrome.","doi":"https://doi.org/10.1038/s41375-018-0348-x","datasets":["JGAD000226"]},{"title":"Unraveling unique features of plasma cell clones in POEMS syndrome with single-cell analysis","doi":"https://doi.org/10.1172/jci.insight.151482","datasets":["JGAD000395"]}],"datasets":["JGAD000226"],"controlledAccessUsers":[{"principalInvestigator":{"ja":"浜田 道昭","en":"Michiaki Hamada"},"affiliation":{"ja":"浜田研究室, 理工学術院, 早稲田大学","en":"Hamada Laboratory, Faculty of Science and Engineering, Waseda University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"RNA標的創薬データベースの構築","en":"Construction of RNA-targeted Drug Discovery Database"},"periodStart":"2023-01-05","periodEnd":"2027-10-31","datasets":["JGAD000226"]},{"principalInvestigator":{"ja":"奥野 龍禎","en":"Tatsusada Okuno"},"affiliation":{"ja":"神経内科学, 大阪大学大学院医学系研究科","en":"Department of Neurology, Osaka University Graduate School of Medicine"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"神経筋疾患の病態解明","en":"Pathophysiological Understanding of Neuromuscular Diseases"},"periodStart":"2024-11-26","periodEnd":"2025-10-30","datasets":["JGAD000226","JGAD000395"]}]}