胚性幹細胞の多能性のための拡張された転写ネットワーク
Jonghwan Kim1, Jianlin Chu, Xiaohua Shen
1Department of Pediatric Oncology, Boston, MA 02115, USA.
Cell
|March 25, 2008
まとめ
研究者は,胚性幹細胞の多能性を制御する重要な転写因子をマッピングしました. 彼らは,遺伝子プロモーターに結合する因子の数が,遺伝子が分化中に活性化するか抑止されるかを決定することを発見しました.
科学分野:
- 幹細胞生物学 幹細胞生物学とは
- エピジェネティクス エピジェネティクス
- トランスクリプション・ファクター・ネットワーク
背景:
- 胚性幹細胞 (ES細胞) は多能性を持ち,任意の細胞型に分化する能力を持っています.
- この重要な状態を維持するために限られた数の転写因子が知られている.
- 多能性を支配する規制ネットワークの包括的な理解が欠けている.
研究 の 目的:
- ネズミのES細胞における9つの重要な転写因子のターゲットプロモーターを世界的に特定する.
- 多能性を維持する規制ネットワークを解明する.
- ES細胞の運命決定における転写因子の役割を理解する.
主な方法:
- 転写因子の結合部位を全ゲノムで特定する.
- マウスのES細胞における遺伝子プロモーターにおける転写因子の占有率の分析.
- 転写因子結合と遺伝子の活性,分化状態の相関.
主要な成果:
- Oct4, Sox2, Klf4, c-Myc, Nanog, Dax1, Rex1, Zpf281, Nac1.1に対する標的プロモーターが特定されました.
- 少数の因子に結合するプロモーターは不活性/抑制され, >4の因子に結合するプロモーターは多能細胞で活性化し,分化時に抑制されることが示された.
- c-Mycの標的を他の標的と区別する再プログラミング因子のトランスクリプションの階層を提案した.
結論:
- プロモーターに結合する転写因子の数は,多能細胞における遺伝子の活性を決定する重要な決定因子である.
- c-Mycのような因子の役割が異なる複雑な転写ネットワークは,多能性を維持する.
- この研究は,多能性と差別化の基礎となるメカニズムを調査するための貴重なリソースを提供します.
関連する概念動画
01:13Induced 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...
02:33Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
01:13Induced 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...
01:06Induced 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...
01:14Maintenance 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...
01:29Somatic 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...