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Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

22.9K
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...
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Introduction to Nuclear Reprogramming01:14

Introduction to Nuclear Reprogramming

1.3K
Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
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Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

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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).
Somatic...
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Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

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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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Forced Transdifferentiation01:28

Forced Transdifferentiation

1.5K
Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial...
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Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

1.4K
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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Selecting and Isolating Colonies of Human Induced Pluripotent Stem Cells Reprogrammed from Adult Fibroblasts
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非ストキャスティックな再プログラミングは,特権のある体細胞状態から生まれます.

Shangqin Guo1, Xiaoyuan Zi2, Vincent P Schulz3

  • 1Department of Cell Biology, Yale University, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA.

Cell
|February 4, 2014
PubMed
まとめ
この要約は機械生成です。

科学者たちは,体細胞を多能性へと再プログラムすることをより速く,非ストキャスティックにすることを可能にする特別な細胞状態を発見しました. このブレークスルーは,超高速な細胞サイクルを持つこれらの特権的な細胞を特定し,利用することによって,誘発された多能性を加速します.

さらに関連する動画

In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
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De Novo Generation of Somatic Stem Cells by YAP/TAZ
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関連する実験動画

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Selecting and Isolating Colonies of Human Induced Pluripotent Stem Cells Reprogrammed from Adult Fibroblasts
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In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
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De Novo Generation of Somatic Stem Cells by YAP/TAZ
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科学分野:

  • 細胞生物学 細胞生物学
  • 発達生物学 発達生物学について
  • 幹細胞の研究について

背景:

  • ヤマナカ因子を使用した somatic cell 再プログラムが誘発性多能性 (iPSC) に至ることは,通常,遅くて非効率的です.
  • このプロセスは,ランダムに発生することを意味するストキャスティックと考えられています.
  • 再プログラミングの効率を高める要因を特定することは,治療的応用において極めて重要です.

研究 の 目的:

  • 非ストキャスティックな再プログラミングを容易にする特定の体細胞状態を特定する.
  • 再プログラミングプロセスにおける細胞サイクル速度の役割を調査する.
  • 細胞サイクルダイナミクスをターゲットにすることで,再プログラミングのボトルネックを克服できるかどうかを判断する.

主な方法:

  • 実験を再プログラムするために,ネズミの血液生成原体とネズミの胚性線維芽細胞 (MEFs) を利用した.
  • 多能性を誘発するためのヤマナカ因子表現を用いた.
  • 細胞サイクル期間と多能性獲得率を分析した.
  • 再プログラム効率と細胞サイクル速度に対するp53ノックダウンの効果を調査した.

主要な成果:

  • 超高速な細胞周期 (約1~3年) を表す血液形成の原始体および線維芽細胞において"特権"の体細胞状態を特定した. 8時間). 8時間).
  • これらの特権的な細胞の子孫は,主に4〜5回の分裂後に非ストキャスティックな方法で多能性を獲得しました.
  • 繊維芽細胞の超高速サイクリングサブポピュレーションは,因子発現の6日後に現れ,p53ノックダウンによって著しく強化されました.
  • この超高速サイクリング集団は,大量再プログラム活動の99%以上を担っていました.

結論:

  • ソマティック細胞の再プログラミングのストキャスティックな性質は,特権的な細胞状態を隔離または誘導することによって克服することができます.
  • 細胞サイクルが急激に進行し,臨界値に達することは,再プログラム効率化における重要なボトルネックです.
  • 細胞サイクルダイナミクスをターゲットにすることは,誘発された多能性およびその治療的可能性を高める有望な戦略を提供します.