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Related Concept Videos

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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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

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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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Lineage Commitment01:21

Lineage Commitment

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Commitment is the  process whereby stem cells:
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Zygotic Development And Stem Cell Formation01:10

Zygotic Development And Stem Cell Formation

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The development of all multicellular organisms starts with the fusion of haploid cells called sperm and egg to form a diploid zygote. A zygote is a totipotent cell that can develop into a complete organism. The zygote undergoes cell division or cleavage to form an 8-cell mass. Until this stage, the cells are spherical, loosely attached, and remain totipotent. Totipotent cells are capable of developing both the embryonic and the extraembryonic tissues. However, as they continue to divide, they...
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Related Experiment Video

Updated: Apr 2, 2026

Protocol for the Direct Conversion of Murine Embryonic Fibroblasts into Trophoblast Stem Cells
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Protocol for the Direct Conversion of Murine Embryonic Fibroblasts into Trophoblast Stem Cells

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Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells.

Hana Benchetrit1, Shay Herman1, Niek van Wietmarschen2

  • 1Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

Cell Stem Cell
|September 29, 2015
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Summary

Transient expression of specific genes in fibroblasts can create trophoblast stem-like cells (iTSCs). This demonstrates that extensive nuclear reprogramming is achievable without inducing pluripotency, challenging previous assumptions in stem cell research.

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Area of Science:

  • Stem cell biology
  • Epigenetics
  • Developmental biology

Background:

  • Induced pluripotent stem cells (iPSCs) are generally indistinguishable from embryonic stem cells (ESCs).
  • Direct cell conversion often results in incomplete reprogramming and functional deficits.
  • The necessity of pluripotency for high-fidelity nuclear reprogramming remains an open question.

Purpose of the Study:

  • To investigate whether pluripotency is a prerequisite for achieving extensive nuclear reprogramming.
  • To determine if direct conversion can yield fully reprogrammed cells without a pluripotent intermediate.

Main Methods:

  • Transient expression of Gata3, Eomes, and Tfap2c in mouse fibroblasts.
  • Generation of transgene-independent trophoblast stem-like cells (iTSCs).
  • Comparative analysis of iTSCs with blastocyst-derived trophoblast stem cells (TSCs) using transcriptomic, methylation, and epigenetic profiling (H3K27ac, H2A.X).
  • In vitro differentiation and in vivo chimera assays to assess functional capacity.

Main Results:

  • Stable, transgene-independent iTSCs were generated from mouse fibroblasts.
  • iTSCs exhibited transcriptional, methylation, and epigenetic profiles highly similar to bona fide TSCs.
  • iTSCs successfully differentiated into trophoectodermal lineages and contributed to placental development in chimera assays.
  • No evidence of a transient pluripotent state was observed during iTSC generation.

Conclusions:

  • Extensive nuclear reprogramming can be achieved independently of pluripotency.
  • Transient expression of specific factors can directly induce a specialized stem cell fate (trophoblast stem cells).
  • This finding challenges the paradigm that pluripotency is essential for complete cellular reprogramming.