多能细胞中复杂的哈普洛缺陷产生了具有DNA甲基化异常和多能诱导缺陷的体细胞
Rachel Lasry1, Noam Maoz1, Albert W Cheng2
1Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Stem cell reports
|October 13, 2023
概括
保持关键多能性基因的两个功能副本至关重要. 在两个多能性基因中同时失去一个等位基因会损害纤维细胞重编程,突出显示干细胞中复杂的哈普洛缺陷.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 发育生物学是发展生物学.
背景情况:
- 完全淘汰多能性基因严重影响胚胎干细胞功能.
- 多能性基因中单个等位基因的丧失通常被认为是无害的.
研究的目的:
- 研究多能细胞中复杂的哈普隆缺陷的存在和影响.
- 为了确定两个多能性基因的同时异构性损失是否会影响细胞重编程.
主要方法:
- 通过同时消除不同多能性基因对 (例如,Nanog+/-;Sall4+/-) 的一个等位基因,生成双重异构基因突变细胞系.
- 评估了衍生纤维细胞的嵌合体贡献和重编程效率.
- 分析了基因表达动态和DNA甲基化模式.
主要成果:
- 双重异构的突变基因系通常对嵌合体有所贡献,但在纤维细胞中显著减少了多能诱导.
- Sall4 和 Nanog 的随机表达不能完全解释重编程延迟.
- 在突变纤维细胞中观察到异常的DNA甲基化模式,这些异常在特定的治疗中是可逆的.
结论:
- 多能细胞需要关键基因的两个完整的等位基因来维持正常功能和高效的重编程.
- 影响重编程的复杂的哈普洛缺陷,可能是由于两个多能性基因的组合异构性损失而产生的.
- 表观遗传失调,特别是异常的DNA甲基化,是观察到的重编程缺陷的基础.
相关概念视频
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
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
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
Induced Pluripotent Stem Cells
4.1K
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...
4.1K
Inheritance of Chromatin Structures
6.3K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.3K
Genomic Imprinting and Inheritance
34.6K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
34.6K


