EZH1による胚性血液生成多能性の調節
Linda T Vo1,2,3, Melissa A Kinney1,2, Xin Liu4
1Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts, USA.
Nature
|January 18, 2018
まとめ
早期の哺乳類の胚は血液形成幹細胞 (HSC) の発達を抑制する. 初期胚のEZH1タンパク質発現を減少させることで,機能性HSCの出現が加速され,EZH1が血液形成の多能性の主要な抑制剤であることを明らかにする.
科学分野:
- 発達生物学
- ヘマトポエシス
- エピジェネティクス
背景:
- 哺乳類の血液細胞系は,多能な造血幹細胞 (HSC) から発生する.
- 早期の哺乳類の胚では,血統制限の祖先がHSCの前に現れ,最終的なHSCは妊娠後期に現れる.
- この発達のタイミングを制御する 分子メカニズムは不明です
研究 の 目的:
- 特にポリコンブ群のタンパク質を対象としたエピジェネティック・サイレンスが,初期胚形成における決定的なHSCの発達を積極的に抑制するという仮説を検証する.
- この抑制を緩和することで,早期の造血祖先で多効性を誘発できるかどうかを判断する.
主な方法:
- ヒトの多能幹細胞におけるポリコンブ群タンパク質EZH1の発現が低下した.
- エズh1欠乏したマウスの胚を分析し,生体内における血球形成原体の発達を観察する.
主要な成果:
- 減少したEZH1発現は,ヒトの多能幹細胞からのマルチリンパ球出力を高めました.
- ネズミの胚におけるEzh1欠乏は,機能的な最終的なHSCの早発を引き起こした.
- これらの発見は,哺乳類の発達初期における血液生成多能性の抑制剤としてEZH1を特定した.
結論:
- EZH1は早期の哺乳類の胚で血液形成の多能性の抑制剤として作用する.
- EZH1媒介による抑制を緩和すると,機能的な最終的なHSCが早期に発生する可能性があります.
- この研究は,血造幹細胞オントゲニスの表遺伝的調節に光を当てています.
関連する概念動画
02:23Master Transcription Regulators
7.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.9K
01:19Multipotency of Hematopoietic Stem Cells
3.9K
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.9K
01:06Multipotency and Niche of Bulge Stem Cell
4.3K
A hair follicle or HF is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe a bulge in the human hair follicle's outer root sheath (ORS). The bulge is present between the sebaceous gland and the arrector pili muscle and is the niche for hair follicle stem cells (HFSCs). The bulge is also a niche for melanocyte stem cells, and their loss results in graying of hair. The HFSCs express Sox9 and Lhx2, which help them maintain stemness and prevent...
4.3K
01:46Epigenetic Regulation
33.9K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.9K
02:14GTPases and their Regulation
9.9K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
9.9K
02:58Regulated Protein Degradation
8.9K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K