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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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Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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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.
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...
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Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

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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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Introduction to Nuclear Reprogramming01:14

Introduction to Nuclear Reprogramming

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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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Forced Transdifferentiation01:28

Forced Transdifferentiation

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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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iPS Cell Differentiation01:22

iPS Cell Differentiation

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The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
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Video Experimental Relacionado

Updated: Jul 19, 2025

A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
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La reprogramación ingenua transitorio corrige las células hiPS funcional y epigenéticamente

Sam Buckberry1,2,3,4, Xiaodong Liu5,6,7,8,9,10,11, Daniel Poppe1,2

  • 1Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.

Nature
|August 16, 2023
PubMed
Resumen
Este resumen es generado por máquina.

La reprogramación de tratamiento ingenuo transitorio (TNT) corrige la memoria epigenética y las aberraciones en las células madre pluripotentes inducidas humanas (células hiPS), haciéndolas más parecidas a las células madre embrionarias humanas (hES). Este nuevo método mejora la diferenciación celular hiPS para aplicaciones biomédicas.

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Área de la Ciencia:

  • La epigenética
  • Biología de las células madre
  • Tecnologías de reprogramación

Sus antecedentes:

  • Las células madre pluripotentes inducidas humanas (células hiPS) sufren cambios epigenéticos significativos, pero conservan diferencias con las células madre embrionarias humanas (hES).
  • Estas discrepancias epigenéticas, incluidas la memoria y las aberraciones, afectan la función de las células hiPS, con mecanismos subyacentes en gran medida desconocidos.

Objetivo del estudio:

  • Caracterizar la aparición y persistencia de diferencias epigenéticas durante la reprogramación de las células hiPS.
  • Desarrollar una nueva estrategia de reprogramación que emule el restablecimiento epigenético embrionario y corrija los defectos epigenéticos de las células hiPS.

Principales métodos:

  • Perfiles de metilación de ADN en todo el genoma durante la reprogramación primada e ingenua.
  • Desarrollo y aplicación de una estrategia de reprogramación de tratamiento ingenuo transitorio (TNT).
  • Análisis del sistema isogénico para evaluar la corrección epigenética y los resultados funcionales.

Principales resultados:

  • Las aberraciones epigenéticas inducidas por la reprogramación surgen a mediados de la reprogramación; La desmetilación del ADN comienza temprano en la reprogramación ingenua.
  • La reprogramación TNT reconfigura la célula de cromatina represiva dependiente del origen (H3K9me3, lamin-B1, metilación CpH) a un estado similar a la célula hES.
  • Las células hiPS reprogramadas con TNT muestran una expresión de elementos transponibles corregida, una expresión génica mejorada y una mayor eficiencia de diferenciación en comparación con las células hiPS convencionales.

Conclusiones:

  • La reprogramación de TNT corrige efectivamente la memoria epigenética y las aberraciones, produciendo células hiPS molecular y funcionalmente similares a las células hES.
  • Esta estrategia no interrumpe la impresión genómica y mejora la diferenciación entre varios tipos de células.
  • La reprogramación TNT ofrece un nuevo estándar potencial para aplicaciones biomédicas y terapéuticas y una herramienta para estudiar la memoria epigenética.