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Videos de Conceptos Relacionados

Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

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 for this...
Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

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 injury repair.
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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...
iPS Cell Differentiation01:22

iPS Cell Differentiation

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.
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

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 cells are...
Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

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 called induced pluripotent stem...

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Video Experimental Relacionado

Updated: Jun 21, 2026

Cell Surface Marker Mediated Purification of iPS Cell Intermediates from a Reprogrammable Mouse Model
10:32

Cell Surface Marker Mediated Purification of iPS Cell Intermediates from a Reprogrammable Mouse Model

Published on: September 6, 2014

El locus Ink4/Arf es una barrera para la reprogramación de las células iPS.

Han Li1, Manuel Collado, Aranzazu Villasante

  • 1Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), 3 Melchor Fernandez Almagro Street, Madrid E-28029, Spain.

Nature
|August 12, 2009
PubMed
Resumen

El silenciamiento del locus Ink4/Arf es crucial para la generación de células madre pluripotentes inducidas (iPS). La inhibición transitoria de este locus mejora significativamente la eficiencia y la cinética de la reprogramación, ofreciendo una estrategia clave para la producción de células iPS.

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Last Updated: Jun 21, 2026

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Área de la Ciencia:

  • La reprogramación celular es la reprogramación celular.
  • La epigenética es la epigenética.
  • Biología de las células madre Biología de las células madre

Sus antecedentes:

  • Los mecanismos de generación de células madre pluripotentes inducidas (iPS) que involucran a Oct4, Klf4 y Sox2 no se comprenden completamente.
  • El locus Ink4/Arf, que codifica los supresores tumorales p16 (Ink4a), p19 (Arf) y p15 (Ink4b), está regulado hacia arriba en las células diferenciadas.
  • El papel de este locus en la reprogramación de la eficiencia es un área crítica de investigación.

Objetivo del estudio:

  • Investigar el papel del locus Ink4/Arf en la reprogramación de las células diferenciadas en células iPS.
  • Determinar si el silenciamiento del locus Ink4/Arf es esencial para la generación eficiente de células iPS.
  • Explorar estrategias terapéuticas para mejorar la producción de células iPS al dirigirse al locus Ink4/Arf.

Principales métodos:

  • Análisis del silenciamiento del locus Ink4/Arf en las células iPS y las células madre embrionarias (ES).
  • Evaluación de la expresión del locus Ink4/Arf durante la reprogramación en diversas condiciones de cultivo celular.
  • Inhibición genética y mediada por shRNA del locus Ink4/Arf para evaluar la eficiencia de la reprogramación.
  • Análisis comparativo de la función del locus Ink4/Arf en células murinas y humanas.
  • Investigación de la regulación del locus Ink4/Arf en células envejecidas y su impacto en la reprogramación.

Principales resultados:

  • El locus Ink4/Arf está completamente silenciado en las células iPS y ES, adquiriendo marcas bivalentes de cromatina.
  • Las condiciones de reprogramación mejoran la expresión Ink4/Arf, lo que requiere su silenciamiento para una eficiente generación de células iPS.
  • La acción cooperativa de Oct4, Klf4 y Sox2 reprime el locus Ink4/Arf, que se correlaciona con los marcadores del tallo.
  • La inhibición genética de Ink4/Arf aumenta significativamente la cinética de la generación celular iPS y el número de colonias.
  • Arf es la barrera primaria en las células murinas (a través de p53/p21), mientras que INK4a es más crítica en los fibroblastos humanos.
  • La regulación al alza de Ink4/Arf relacionada con la edad reduce la eficiencia de la reprogramación, que es rescatada por la inhibición del locus.

Conclusiones:

  • El silenciamiento del locus Ink4/Arf es un paso que limita la velocidad en la reprogramación celular de iPS.
  • La inhibición transitoria del locus Ink4/Arf es una estrategia prometedora para mejorar la generación de células iPS.
  • Comprender la regulación Ink4/Arf proporciona información sobre la plasticidad celular y el envejecimiento.
  • Targeting Ink4/Arf ofrece una potencial vía terapéutica para las aplicaciones de medicina regenerativa.