ゲメット由来DNAメチル化を維持する基底状態の雌性ES細胞の誘導
Masaki Yagi1, Satoshi Kishigami2, Akito Tanaka1
1Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.
Nature
|July 27, 2017
まとめ
マウス胚性幹細胞 (ES細胞) の誘導に用いられる2つの小分子 (2i) は,ゲノムインプリントを消去する. これらの細胞は微分化できるが 発達上の欠陥を示し 改良された誘導方法の必要性を強調している.
科学分野:
- 発達生物学
- エピジェネティクス
- 幹細胞生物学
背景:
- 2つの小分子 (2i) と白血病抑制因子 (LIF) は,胚性幹細胞 (ES細胞) の誘導を促進し,歯類における基底状態の多能性を促進する.
- 雌マウスのES細胞を2i/LIFで誘導すると,広範なDNA低甲基化とゲノムインプリントの消去が生じます.
研究 の 目的:
- 2i/LIFが雌マウスのES細胞のDNAメチル化,インプリント化,発達の可能性に与える影響を調査する.
- エピジェネティックマークと発達能力を維持しながら,多能性を維持する誘導条件を特定する.
主な方法:
- 2i/LIFの存在で雌マウスのES細胞の誘導
- インプリント制御領域 (ICR) を含むDNAメチル化分析
- テトラプロイド胚補充と核移植の測定は,発達の可能性を評価するものです.
主要な成果:
- 2i/LIF治療は,全局的なDNA低メチル化と雌性ES細胞のゲノムインプリントの大規模な消去を引き起こしました.
- 低メチル化にもかかわらず,早期通過の2i/LIF ES細胞は体細胞に微分化し,新たなDNAメチル化を必要とする.
- しかし,ほとんどのICRは分化細胞で非メチル化であり,2i/LIF ES細胞は胚および胎盤の発達障害を示した.
- 長い培養は,培養条件に関係なくICR脱メチル化をもたらした.
- 2i/LIFのような転写プロファイルを持つ雌性ES細胞を生成する特定の誘導条件が特定されたが,DNAメチル化と発達の可能性を保持している.
結論:
- 2i/LIFの使用は,インプリントの消去を含む,女性ES細胞の誘導に際し,発達の可能性を損なう,表層遺伝的異常を引き起こす.
- ES細胞の発達能力を維持するために,ゲメット由来DNAメチル化の保存が不可欠です.
- この研究は,移植前の胚の内部の細胞質を模倣する女性のES細胞を導き出すための洞察を提供し,発達研究のためのより堅固なモデルを提供します.
関連する概念動画
01:14Maintenance of the ES Cell State
2.8K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.8K
03:17Inheritance of Chromatin Structures
7.7K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
7.7K
00:57Embryonic Stem Cells
5.5K
Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
5.5K
02:30Genomic Imprinting and Inheritance
37.7K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
37.7K
01:24Methods of Nuclear Reprogramming
2.2K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
2.2K
01:10Zygotic Development And Stem Cell Formation
7.0K
The development of all multicellular organisms starts with the fusion of haploid cells called sperm and egg to form a diploid zygote. A zygote is a totipotent cell that can develop into a complete organism. The zygote undergoes cell division or cleavage to form an 8-cell mass. Until this stage, the cells are spherical, loosely attached, and remain totipotent. Totipotent cells are capable of developing both the embryonic and the extraembryonic tissues. However, as they continue to divide, they...
7.0K