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Somatic to iPS Cell Reprogramming01:29

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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...
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Chromatin Modification in iPS Cells01:32

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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.
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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...
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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).
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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
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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...
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相关实验视频

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Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle
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高衰老限制了体细胞重编程期间的细胞可塑性.

Bogdan B Grigorash1,2, Dominic van Essen1, Guixian Liang3,4

  • 1Institute for Research on Cancer and Aging of Nice (IRCAN), Université Côte d'Azur, INSERM, CNRS, Nice, France.

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|August 31, 2023
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概括

移除衰老细胞可以增强体细胞的四因素重编程 (4FR),使其变成类似于全能干细胞的干细胞. 这一过程通过促进细胞可塑性和逆转衰老标志物,使老化的组织恢复青春.

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科学领域:

  • 细胞重新编程的细胞重编程.
  • 生物老龄化生物学
  • 干细胞研究的研究.

背景情况:

  • 四因素重编程 (4FR) 在体外和体内都取得了进展,但其与细胞衰老的相互作用尚未得到充分研究.
  • 衰老是一种不可逆转的细胞循环停止状态,与衰老和组织功能障碍有关.

研究的目的:

  • 为了研究衰老细胞在4FR.中的作用.
  • 探索操纵衰老的潜力,以实现再生目的.

主要方法:

  • 基因和化学耗尽p16高衰老细胞.
  • 身体细胞的四个因素重编程.
  • 分析多能性标记物,双细胞胚胎状态标记物,状体形成,以及胚胎/胚胎外血统贡献.
  • 研究尼古丁胺N-甲基转移酶调节和S-adenosyl-L-methionine水平的研究.
  • 部分4F表观遗传重编程在老年小鼠和没有衰老细胞枯竭.

主要成果:

  • 耗尽p16高衰老细胞使4FR成为表达多能和双细胞胚胎标记的全能类干细胞.
  • 这些重新编程的细胞形成了植入能力强的体,并为胚胎血统做出了贡献.
  • 尼古丁胺N-甲基转移酶的衰老依赖调节被确定为4FR和胚胎外潜力的关键.
  • 部分4FR与衰老细胞枯竭相结合,在老小鼠中逆转了肝脏衰老标志物.

结论:

  • p16高衰老细胞在4FR期间限制细胞可塑性.
  • 衰老细胞的枯竭促进了类似于 totipotent 的状态和组织复发.
  • 针对衰老是一种可行的策略,可以增强重编程和打击衰老.