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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

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Induced Pluripotent Stem Cells01:06

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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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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.
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La reprogramación no estocástica desde un estado privilegiado de la célula somática.

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
Resumen
Este resumen es generado por máquina.

Los científicos descubrieron un estado celular especial que hace que la reprogramación de las células somáticas a la pluripotencia sea más rápida y no estocástica. Este avance acelera la pluripotencia inducida mediante la identificación y utilización de estas células privilegiadas con ciclos celulares ultrarrápidos.

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Área de la Ciencia:

  • Biología celular Biología celular.
  • Biología del desarrollo Biología del desarrollo.
  • Investigación con células madre.

Sus antecedentes:

  • La reprogramación de las células somáticas a la pluripotencia inducida (iPSC) utilizando factores Yamanaka es típicamente lenta e ineficiente.
  • El proceso es ampliamente considerado estocástico, lo que significa que ocurre al azar.
  • La identificación de factores que mejoran la eficiencia de la reprogramación es crucial para las aplicaciones terapéuticas.

Objetivo del estudio:

  • Identificar estados específicos de las células somáticas que facilitan la reprogramación no estocástica.
  • Investigar el papel de la velocidad del ciclo celular en el proceso de reprogramación.
  • Para determinar si los cuellos de botella de reprogramación pueden ser superados por la orientación de la dinámica del ciclo celular.

Principales métodos:

  • Se utilizaron progenitores hematopoyéticos murinos y fibroblastos embrionarios de ratón (MEF) para experimentos de reprogramación.
  • Utilizó la expresión del factor Yamanaka para inducir la pluripotencia.
  • Se analizaron la duración del ciclo celular y las tasas de adquisición de pluripotencia.
  • Investigó el efecto de la eliminación de p53 en la eficiencia de la reprogramación y la velocidad del ciclo celular.

Principales resultados:

  • Se identificó un estado celular somático "privilegiado" en progenitores hematopoyéticos y fibroblastos que exhiben ciclos celulares ultrarrápidos (aprox. 8 horas). durante el día.
  • La progenie de estas células privilegiadas predominantemente adquirió pluripotencia de una manera no estocástica después de 4-5 divisiones.
  • Una subpoblación de ciclos ultrarrápidos en los fibroblastos surgió después de 6 días de expresión de factores, significativamente mejorada por el knockdown de p53.
  • Esta población de ciclistas ultrarrápidos fue responsable de más del 99% de la actividad de reprogramación masiva.

Conclusiones:

  • La naturaleza estocástica de la reprogramación celular somática puede superarse aislando o induciendo un estado celular privilegiado.
  • La progresión acelerada del ciclo celular hasta un umbral crítico es un cuello de botella clave en la eficiencia de la reprogramación.
  • Dirigirse a la dinámica del ciclo celular ofrece una estrategia prometedora para mejorar la pluripotencia inducida y su potencial terapéutico.