核S-ニトロシレーションは,多能性を誘導するための最適なゾーンを定義します
Palas K Chanda1, Shu Meng1, Jieun Lee2
1Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, TX (P.K.C., S.M., K.C., J.P.C.).
Circulation
|August 16, 2019
まとめ
生まれながらの免疫活性化と窒素酸化物 (NO) 生成は,表遺伝的可塑性のための最適の"ゴールドロックスゾーン"を作り,誘発された多能幹細胞の生成を強化します. このバランスは 核の再プログラムと細胞の運命を決定します
科学分野:
- エピジェネティクスと細胞生物学
- 生まれつきの免疫 と 幹細胞 再プログラム
背景:
- 細胞自律の先天的な免疫シグナリングは,核再プログラムによる多能性への表遺伝子変異に影響を与えます.
- 以前の研究では,誘導性窒素酸化物 (NO) 合成によるS- ニトロシル化が細胞変異における役割を示した.
研究 の 目的:
- 核再プログラムにおけるS-ニトロシレーションの役割を調査する.
- 生まれながらの免疫活性化,NO生成,および誘発性多能幹細胞 (iPSC) の産出との関係を決定する.
主な方法:
- ネズミの胚性線維細胞におけるドキシサイクリン誘導ヤマナカ因子の発現を活用した.
- 誘導可能なNO合成の遺伝子/薬学的抑制,タンデム・マス・タグ,ChIP-qPCR,サイト・ディレクテッド・ミュータジェネシス,およびマイクロコック・ヌクレアース・アッセイを用いた.
主要な成果:
- NF-κBの活性化,NO生成,S-ニトロシル化によって定義される,先天的な免疫活性化の最適なゾーンは,iPSCの生産性を最大化します.
- 誘導可能なNO合成の抑制はDNAのアクセシビリティと iPSCの生成を減少させます.
- MTA3を含む核タンパク質のS- ニトロシル化により,NuRD複合体の活性が低下し,DNAのアクセシビリティと再プログラミングに影響する.
結論:
- DNAのアクセシビリティとiPSCの生産性は,先天的な免疫活性化とNO生成の程度に依存しています.
- 炎症シグナル伝達と表遺伝的可塑性の"ゴールドロックスゾーン"は細胞の運命と表型流動性に影響する.
関連する概念動画
01:13Induced Pluripotent Stem Cells
27.3K
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...
27.3K
01:06Induced Pluripotent Stem Cells
5.4K
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...
Somatic...
5.4K
02:29Hybrid Zones
21.8K
Hybrid zones are narrow regions where two closely related species interact, mate, and produce hybrids. Relative to either parent species, hybrids may possess distinct phenotypic or genetic differences that impact their survival and reproductive success. The genetic variances introduced by hybridization influence species diversity and speciation processes within the hybrid zone.
21.8K
02:50Nuclear Fission
12.3K
Many heavier elements with smaller binding energies per nucleon can decompose into more stable elements that have intermediate mass numbers and larger binding energies per nucleon—that is, mass numbers and binding energies per nucleon that are closer to the “peak” of the binding energy graph near 56. Sometimes neutrons are also produced. This decomposition of a large nucleus into smaller pieces is called fission. The breaking is rather random with the formation of a large...
12.3K
03:18Nuclear Stability
22.9K
Protons and neutrons, collectively called nucleons, are packed together tightly in a nucleus. With a radius of about 10−15 meters, a nucleus is quite small compared to the radius of the entire atom, which is about 10−10 meters. Nuclei are extremely dense compared to bulk matter, averaging 1.8 × 1014 grams per cubic centimeter. If the earth’s density were equal to the average nuclear density, the earth’s radius would be only about 200 meters.
To hold positively charged protons together...
To hold positively charged protons together...
22.9K
02:45Nuclear Fusion
33.7K
The process of converting very light nuclei into heavier nuclei is also accompanied by the conversion of mass into large amounts of energy, a process called fusion. The principal source of energy in the sun is a net fusion reaction in which four hydrogen nuclei fuse and ultimately produce one helium nucleus and two positrons.
A helium nucleus has a mass that is 0.7% less than that of four hydrogen nuclei; this lost mass is converted into energy during the fusion. This reaction produces about...
A helium nucleus has a mass that is 0.7% less than that of four hydrogen nuclei; this lost mass is converted into energy during the fusion. This reaction produces about...
33.7K