昼夜时钟CRY1调节多能干细胞身份和体细胞重编程
Shogo Sato1, Tomoaki Hishida2, Kenichiro Kinouchi3
1Center for Epigenetics and Metabolism, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA; Center for Biological Clocks Research, Department of Biology, Texas A&M University, College Station, TX, USA.
Cell reports
|June 1, 2023
概括
昼夜抑制剂CRY1在多能干细胞 (PSC) 中发挥着独特的作用,维持自我更新和代谢特征. CRY1对于有效的诱导PSC重编程和决定干细胞身份至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 干细胞生物学 干细胞生物学
背景情况:
- 代谢条件影响昼夜时钟控制的信号通路.
- 多能干细胞 (PSC) 的代谢特征与时钟功能之间的联系尚不清楚.
研究的目的:
- 研究PSC中昼夜抑制器CRY1的非规范性功能.
- 确定CRY1在PSC自我更新,代谢特征和诱导PSC (iPSC) 重编程中的作用.
主要方法:
- 在PSCs中,在代谢重编程 (AMPK失活,SREBP1激活) 期间评估了CRY1积累.
- 执行功能测试以评估CRY1对PSC维护的必要性.
- 进行了CRY1.1的全基因组占用分析.
- 在iPSC重编程过程中分析了CRY1缺乏细胞中的基因表达特征.
主要成果:
- 在代谢重编程过程中,CRY1在PSC中积累.
- CRY1对于PSC的自我更新,殖民地组织和代谢特征至关重要.
- CRY1与参与PSCs发育和分化的调节基因结合.
- 失去CRY1会损害iPSC重编程效率,并改变基因表达.
结论:
- CRY1在PSC中发挥着关键的,非正规的作用,与其在体细胞中的功能不同.
- CRY1是PSC身份的关键调节者,影响自我更新和代谢平衡.
- CRY1在功能上涉及到多能重编程和早期发育 (本体发生).
相关概念视频
Somatic to iPS Cell Reprogramming
2.2K
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...
2.2K
Circadian Rhythms and Gene Regulation
4.1K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.1K
Methods of Nuclear Reprogramming
1.9K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.9K
Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
Maintenance of the ES Cell State
2.2K
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...
2.2K
Induced Pluripotent Stem Cells
4.2K
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...
4.2K


