胚性幹細胞の微分化の内在的な移行が,神経原始細胞へと変化する
Daisuke Kamiya1, Satoe Banno, Noriaki Sasai
1Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Nature
|February 18, 2011
まとめ
亜鉛指タンパク質Zfp521は,胚性幹細胞 (ES) の神経分化を本質的に駆動する. その発現は,表皮質細胞を,外部信号なしで神経皮質の原始細胞に変換するのに極めて重要です.
科学分野:
- 発達生物学 発達生物学について
- 幹細胞生物学 幹細胞生物学
- 分子神経科学は分子神経科学である.
背景:
- 胚性幹細胞 (ES) が神経細胞に微分化することは,根本的なプロセスです.
- 内在神経の運命を決定する細胞内メカニズムは,ほとんど不明のままである.
- これらのメカニズムを理解することは,再生医療のための幹細胞の分化制御の鍵です.
研究 の 目的:
- ネズミのES細胞の固有の神経分化を制御する細胞内要因を解明する.
- エピブラストから神経外皮原体への移行に関与する重要なタンパク質を特定する.
- 神経の運命を開始するZfp521の役割を調査する.
主な方法:
- ES細胞の分化中のZfp521発現の分析.
- 強制的なZfp521発現を含む機能獲得の研究.
- Zfp521の枯渇による機能喪失に関する研究.
- Zfp521のp300のような共同活性化剤との相互作用の調査.
- 初期の神経遺伝子の活性化の評価.
主要な成果:
- Zfp521は,BMP4.4が存在しない場合,ES細胞の分化中に本質的に誘発されます.
- 強制的なZfp521発現は,BMP4が存在する場合でも,神経変換を促進します.
- Zfp521の枯渇はニューラル変換を阻害し,細胞がエピブラスト段階で停止する.
- Zfp521は,共活性化器p300を介して神経遺伝子を直接活性化します.
結論:
- Zfp521は,ES細胞の固有神経分化に不可欠かつ十分である.
- Zfp521の細胞内的な発現と活性化機能は,表皮質から神経外皮原始体への移行に不可欠です.
- Zfp521は,幹細胞におけるニューラル運命を決定する鍵となる分子スイッチを表しています.
関連する概念動画
01:30Neurulation
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the anterior...
01:51Determination
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...
01:22iPS Cell Differentiation
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
01:28Forced Transdifferentiation
Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial transdifferentiation occurs...
Artificial transdifferentiation occurs...