{"id":"hum0433","version":1,"url":"https://humandbs.dbcls.jp/research/hum0433/v1","datePublished":"2024-09-25","versions":[{"version":1,"datePublished":"2024-09-25"}],"title":{"ja":"ヒト胎盤幹細胞の樹立と細胞特性に関する基礎的研究 / ヒト胎盤栄養膜細胞株の樹立と細胞特性に関する研究","en":"Derivation of human trophoblast stem cells and analysis of those characteristics / Derivation of human trophoblast stem cells and those epigenomic landscape"},"summary":{"aims":{"ja":"ヒト胎盤絨毛細胞に関する研究は、これまで妊娠初期の胎盤組織を用いた数日間の培養（初期培養）や、絨毛がん細胞より得られたさまざまなデータから正常細胞での機能を類推してきた。しかし、初代培養法では培養期間が短いため十分な解析が困難であり、また、絨毛がん細胞では、様々な分子機構が破綻しており、研究結果をそのまま正常絨毛細胞での機能とするには無理がある。本研究では、ヒト胎盤の基礎的研究のモデルとして、ヒト胎盤未分化栄養膜細胞株を樹立し、その細胞特性を明らかにする。","en":"Trophoblast cells play an essential role in the interactions between the fetus and mother, however, the in vitro model to investigate the nature of human trophoblasts has been limited. In this study, we derived human trophoblast stem cells (hTSCs) from first-trimester cytotrophoblasts (CTs) and blastocysts and revealed their epigenomic landscapes including histone modifications, transcription factor binding sites, and long-range chromatin interactions."},"methods":{"ja":"妊娠初期（妊娠 7~10 週）の人工妊娠中絶術の際に得られた胎盤組織と脱落膜組織、ならびに正常および妊娠高血圧症候群患者の分娩後の胎盤組織と脱落膜組織を回収し、磁気細胞分離法を用いて栄養膜細胞のみを高純度（90%以上）に分離する。分離した細胞に数種類の増殖因子を加え、細胞培養する。また、破棄予定のヒト受精卵（ブラスト胚）よりヒト胎盤幹細胞株（hTSC）を樹立し、細胞増殖特性（細胞増殖能、細胞増加時間の測定、アポトーシス、細胞同期、細胞表面抗原、分泌蛋白、分化能）について解析する。併せて、栄養膜細胞、受精卵から樹立したhTSC、および栄養膜細胞から樹立したhTSCを用いて、RNA-seqやエピゲノム（ヒストン修飾、転写因子結合、クロマチン立体構造）解析を実施する。","en":"First-trimester placentas are obtained from elective termination of pregnancies. Placenta and blastocysts after delivery are obtained from the normal and hypertensive disorders of pregnancy (HDP) donors. Whole placental villi are enzymatically digested, and CT cells were immunomagnetically purified using a PE-conjugated anti-ITGA6 antibody. CTs were cultured in TS medium containing EGF, CHIR99021, A83-01, VPA, and Y27632. Differentiated and undifferentiated human trophoblast stem cells (hTSCs) are used to investigate mRNA expression, epigenomic features, proliferation, protein expression, and trophoblast functions."},"targets":{"ja":"人工妊娠中絶術後の初期胎盤および破棄予定の受精卵、正常および妊娠高血圧症候群患者の分娩後の胎盤","en":"Placenta after artificial abortion or after delivery and a discarded blastocyst"},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"発現\nクロマチン構造\nヒストン修飾\nメチル化","en":"Expression profiling, Chromatin structure profiling, Histone modification profiling, Methylation profiling"},"targets":{"ja":"人工妊娠中絶術後の初期胎盤：1検体\n受精卵：1検体\n妊娠高血圧症候群：14症例\n正常妊娠：12名\n（日本人）","en":"placenta after artificial abortion: 1 sample\ndiscarded blastocyst: 1 sample\nhypertensive disorders of pregnancy: 14 cases\nnormal pregnancy: 12 subjects\n(Japanese)"},"typeOfData":{"ja":"NGS\n（RNA-seq、ChIP-seq、Hi-C、small RNA-seq、CUT&TAG-seq、Methyl-seq）","en":"NGS\n(RNA-seq, ChIP-seq, Hi-C, small RNA-seq, CUT&TAG-seq, Methyl-seq)"}},"releaseNote":{"ja":"人工妊娠中絶術後の初期胎盤と脱落膜組織から樹立したヒト胎盤幹細胞、および、受精卵から樹立したヒト胎盤幹細胞株、ならびに、正常および妊娠高血圧症候群患者の分娩後の胎盤組織と脱落膜組織から分離した栄養膜細胞および栄養膜細胞から樹立したヒト胎盤幹細胞株より抽出したDNA/RNAを用いたRNA-seq、ChIP-seq、Hi-C、small RNA-seq、CUT&TAG-seq、Methyl-seq解析データをfastq、txt、bigwig、bedpeファイルにて提供する。","en":"DNAs/RNAs extracted from cytotrophoblast cells purified from placenta after artificial abortion or delivery and trophoblast stem cells derived from a blastocyst or cytotrophoblast cells were used for the RNA-seq, ChIP-seq, Hi-C, small RNA-seq, CUT&TAG-seq and Methyl-seq analyses. Fastq, txt, bigwig, and bedpe files are provided."},"dataProviders":[{"name":{"ja":"小林 枝里","en":"Eri H Kobayashi"},"organization":{"name":{"ja":"東北大学大学院 医学系研究科 環境遺伝医学総合研究センター（情報遺伝学分野）","en":"Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine"}}}],"researchProjects":[],"grants":[{"title":{"ja":"ヒト胎盤の発生・分化に関する理解と臓器チップモデルの作製","en":"Elucidation of the mechanisms underlying human placental development and design of a placenta-on-a-chip platform"},"agency":{"ja":"日本医療研究開発機構（AMED） 革新的先端研究開発支援事業","en":"Advanced Research & Development Programs for Medical Innovation, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP19gm1310001"]}],"relatedPublications":[{"title":"Derivation of Human Trophoblast Stem Cells","doi":"https://doi.org/10.1016/j.stem.2017.11.004","datasets":["JGAD000789","JGAD000790","JGAD000797","E-GEAD-665","E-GEAD-667"]},{"title":"CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development","doi":"https://doi.org/10.1073/pnas.2311372120","datasets":["JGAD000789","E-GEAD-665"]}],"datasets":["JGAD000789","E-GEAD-665","JGAD000790","E-GEAD-667","JGAD000797"],"controlledAccessUsers":[]}