植入後のエピブラストの多能性の胚性幹細胞への表皮遺伝的逆転
Siqin Bao1, Fuchou Tang1, Xihe Li2
1Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
Nature
|October 10, 2009
まとめ
研究者らは,先端のエピブラスト細胞を,表遺伝的障壁を克服して,胚性幹細胞のような細胞 (rESCs) に再プログラムした. これらの再プログラムされた細胞は,キメラの組織と生殖細胞に寄与することができ,多能性の再獲得の可能性を示唆します.
科学分野:
- 発達生物学 発達生物学について
- エピジェネティクス エピジェネティクス
- 幹細胞生物学 幹細胞生物学
背景:
- 多能性は,原始的なエクトダーマで確立され,発達中に不可逆的に失われます.
- DNAメチル化やX不活性化などの表遺伝的変化は,逆転を防ぐ障壁を作り出します.
- エピブラスト幹細胞 (EpiSCs) は胚性幹細胞 (ESCs) と異なっており,LIF-STAT3シグナル伝達に耐火性があります.
研究 の 目的:
- 発達したエピブラスト細胞を,ESCに似た多能状態に再プログラムする.
- エピジェネティック再プログラムプロセスとその結果を調査する.
- 再プログラムされた細胞の発達可能性を評価する.
主な方法:
- LIF-STAT3信号を用いて,マウスの胚 (胚性日5.5-7.5) からの高度なエピブラスト細胞を再プログラムする.
- DNA脱メチル化とX染色体再活性化を含む表遺伝的変化を分析する.
- 再プログラムされた細胞がキメラに与える貢献を評価する.
主要な成果:
- LIF-STAT3.3への反応として,エピブラスト細胞をES細胞のような細胞 (rESCs) に再プログラムすることに成功した.
- DNA脱メチル化とX再活性化を含む,エピブラスト細胞のエピジェネティックメモリの消去が実証されています.
- 再プログラムされたrESCは,エピブラストとEpiSCとは異なり,キメラの体組織と生殖細胞に寄与しました.
結論:
- 信号誘発によるエピジェネティック再プログラミングは,発達上の障壁を克服し,多能性を回復することができます.
- 再プログラムされたエピブラスト幹細胞 (rESC) は,すべての細胞系統に寄与する能力を回復します.
- この研究は,多能性の維持と再獲得のメカニズムについての洞察を提供します.
さらに関連する動画
関連する概念動画
Somatic to iPS Cell Reprogramming
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...
Methods of Nuclear Reprogramming
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 injury repair.
Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore called induced pluripotent stem...
Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Somatic cells are...
Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Maintenance of the ES Cell State
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...


