WNT-SHH対抗性は,ニッチ形成前に幹細胞を特定し拡張する
Tamara Ouspenskaia1, Irina Matos1, Aaron F Mertz1
1Robin Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Cell
|January 16, 2016
まとめ
幹細胞 (SCs) は,非対称な細胞分裂によって,そのニッチとは独立して指定され,調節される. このプロセスは 子細胞が幹細胞か 先祖細胞になるかを決定し 増殖と分化を制御します
科学分野:
- 発達生物学
- 幹細胞生物学
- 細胞シグナリング
背景:
- 成人幹細胞 (SC) の維持と分化は,伝統的にニッチ由来信号によって制御されていると考えられています.
- SCの仕様と規制の開始を規定する正確なメカニズムは,まだ活発な調査の分野です.
研究 の 目的:
- 幹細胞 (SC) の特異化と調節のためのニッチ独立メカニズムを調査する.
- 髪の芽の発達中のSCの早期の運命決定におけるWNTとSHHの役割を解明する.
主な方法:
- 免疫光顕微鏡
- ライブイメージング技術
- 遺伝子操作と系統追跡
- 細胞サイクル分析
- 子宮内のレンチウイルス転移
主要な成果:
- 発達中の毛芽の非対称な細胞分裂は,差異的なWNTとSHHシグナル伝達によってSCを生成する.
- 低WNTシグナルを持つ超基礎の娘はSCになり,パラクリンSHHに反応し,対称的に膨張する.
- 高いWNTシグナリングを持つ基礎の娘は,緩やかなサイクル,非対称な分割を維持し,SHHに反応しない一方,祖先になります.
- このメカニズムは,初期のSCを特定し,その数を制限する前に拡大を促進します.
結論:
- 幹細胞の運命と調節は,内在的,ニッチ独立の非対称な細胞分裂によって開始することができます.
- 非対称的分裂中の微分WNTおよびSHH信号は,子細胞の運命を決定し,幹細胞または祖先細胞を確立します.
- この内在的なメカニズムは 幹細胞の集団が最初に特定され その後 開発中に制御される方法についての新しい理解を提供します
関連する概念動画
01:26Stem Cell Niche
6.6K
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
6.6K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.6K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.6K
01:06Multipotency and Niche of Bulge Stem Cell
4.4K
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...
4.4K
02:54Canonical Wnt Signaling Pathway
10.9K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.9K
02:54Canonical Wnt Signaling Pathway
2.6K
2.6K
01:41Non-Canonical Wnt Signaling Pathways
8.6K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.6K