Name: how nuclear reprogramming changes cell fate
Uploaded: 2023-04-30T12:17:55.000Z
Duration: 1 min 24 s
Channel: JoVE

K12 Standards

Tennessee Academic Standards

High School

Biology

links-among-engineering-technology-science-and-society

Links Among Engineering, Technology, Science, and Society

BIO1.ETS2.3

Methods of Nuclear Reprogramming

A cell fate can be reversed using three different cellular or nuclear reprogramming methods.
In somatic cell nuclear transfer or SCNT, a nucleus from a somatic cell is grafted into an enucleated oocyte.
Transcription factors present in the oocyte cytoplasm promote the expression of embryonic genes and trigger cell division to generate a blastocyst.
The inner cell mass of the blastocyst serves as a source of pluripotent stem cells, which can give rise to specialized cell types.
In cell fusion, two different types of cells are artificially fused together using electric pulses, generating a hybrid cell that displays a combined phenotype.
For example, the fusion of a B cell, a lymphocyte, with a myeloma cell, a cancerous plasma cell, generates a hybrid cell that can both proliferate indefinitely and produce antibodies.
In the transcription factor transduction method, retroviral vectors are used to deliver genes, such as Oct4 and Sox2 to the somatic cells.
The expression of these transcription factors transforms the somatic cell into an induced pluripotent stem or iPS cell.

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&#8217;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 &#8212; developing patient-specific cells for injury repair.
Epigenetic Changes
The prerequisite for successful nuclear reprogramming involves the efficient uncoiling of the genomic DNA inside the nucleus that allows access to regulatory proteins. This is achieved through chromatin decondensation and histone modification that includes acetylation, methylation, and phosphorylation. In somatic cell nuclear transfer (SCNT), the histone modification pattern in the chromatin of a transplanted nucleus changes to that of the oocyte. These changes are enforced by&#160;transcription factors present in the oocyte cytoplasm. For example, oocyte-specific B4 or H1foo histone linkers replace the H1 histone and promote changes in gene expression patterns.
Yamanaka Factors
In 2006, Shinya Yamanaka discovered the Oct-4, Sox-2, Klf-4, and c-Myc transcription factors, referred to as Yamanaka factors, that are highly expressed in embryonic stem (ES) cells. The transcription factor transduction method reprograms the nucleus by overexpressing these transcription factors, thus inducing embryonic gene expression in somatic cells. These transformed cells are called induced pluripotent stem cells or iPSCs. The Oct-4 (octamer-binding transcription factor 4) is a protein encoded by the POU5F1 human gene. It plays a vital role in deciding the fate of the inner mass and embryonic stem cells and helps them to maintain pluripotency during embryonic development. The sex-determining region Y-box 2, referred to as Sox-2, plays an essential role in maintaining the self-renewal potential in ES cells. Klf-4 or Kruppel-like factor 4 belongs to the KLF family of zinc finger transcription factors and is majorly involved in the proliferation and differentiation of stem cells. c-Myc is the transcription factor belonging to the Myc family of protooncogenes, and it has an important role in cellular proliferation and metabolism.

Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell&#8217;s original ...

Education

JoVE Core

Cell Biology

Unit 1

Regeneration and Repair

KEY TERMS AND CONCEPTS

how nuclear reprogramming changes cell fate

Nuclear reprogramming changes one cell type into another by epigenetic changes that shift gene expression. Epigenetic changes do not alter the DNA sequence itself. Instead, they change which genes a cell turns on or off. This process has uses in reproductive cloning for livestock propagation and in regenerative medicine, where patient-specific cells may help with injury repair.

A key step in nuclear reprogramming is opening the DNA inside the nucleus so regulatory proteins can reach it. Cells do this through chromatin decondensation, which loosens tightly packed DNA. Histone modification also helps, including acetylation, methylation, and phosphorylation. In somatic cell nuclear transfer, or SCNT, the histone pattern of a transplanted nucleus shifts to match the oocyte, the egg cell. Transcription factors in the oocyte cytoplasm drive these changes. Oocyte-specific B4 or H1foo histone linkers can replace the H1 histone and help change gene expression patterns.

Another major route uses the Yamanaka factors, discovered by Shinya Yamanaka in 2006. These factors are Oct-4, Sox-2, Klf-4, and c-Myc. They are highly expressed in embryonic stem cells. In the transcription factor transduction method, these proteins are overexpressed in somatic cells, which reprograms the nucleus and induces embryonic gene expression. The transformed cells are called induced pluripotent stem cells, or iPSCs.

Each Yamanaka factor has a specific role. Oct-4, also called octamer-binding transcription factor 4, is encoded by the POU5F1 human gene and helps decide the fate of the inner mass and embryonic stem cells. It also helps maintain pluripotency during embryonic development. Sox-2 supports self-renewal in embryonic stem cells. Klf-4, or Kruppel-like factor 4, is involved in stem cell proliferation and differentiation. c-Myc belongs to the Myc family of protooncogenes and has an important role in cell proliferation and metabolism.

How Nuclear Reprogramming Changes Cell Fate

how-nuclear-reprogramming-changes-cell-fate

overview of regeneration and repair

How Tissues Regrow and Heal After Injury

Regeneration and repair are two ways the body responds to injury, disease, and aging. Regeneration replaces damaged tissue with new growth that restores the original structure and function. Repair usually leaves a fixed tissue pattern and forms a scar. Scars do not usually bring back full tissue function, and the injured area may still look or act abnormal. Animals show very different levels of regeneration. Some, like salamanders, have specialized stem cells that help them regrow fully...

phases of wound repair

How Blood Clots Support Wound Healing

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whole body regeneration

Planarian Regeneration and Body Patterning

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liver regeneration

How the Liver Repairs Itself

The liver can repair itself after injury, and this process depends on several specialized liver cells. The liver also has key jobs in metabolism. It stores and redistributes carbohydrates, fats, and vitamins. It also releases bile salts, which help digest food and remove toxic metabolites from the body. The liver contains four major cell types: hepatocytes, stellate cells, Kupffer cells, and sinusoidal endothelial cells. Hepatocytes are large, polyhedral epithelial cells. They store glycogen,...

stem cell therapy for tissue regeneration

stem-cell-therapy-for-tissue-regeneration

Stem Cell Repair in Blood and Tissues

Stem cell therapy is used in regenerative medicine to repair damaged tissues and organs and help restore function. Stem cells can multiply and change into different tissue types, which makes them useful for tissue repair. One common example is hematopoietic stem cell transplantation, which is used in blood cancer treatment to replace damaged bone marrow and rebuild healthy blood cells. Two main stem cell types are used in stem cell therapy: adult stem cells and embryonic stem cells, or ESCs.

introduction to nuclear reprogramming

Nuclear Reprogramming in Cloning and Stem Cells

Nuclear reprogramming changes the gene expression of one cell type to match another cell type. It often shifts a differentiated cell into a more undifferentiated state. This process is important during development, morphogenesis, tissue regeneration, and malignancy. Cells can also be reprogrammed with laboratory methods. These include nuclear transfer, induced pluripotency, and cell fusion. Scientists use these approaches in molecular medicine, biotechnology, and oncology. A classic early...

Nuclear reprogramming changes one cell type into another by epigenetic changes that shift gene expression. Epigenetic changes do not alter the DNA sequence itself. Instead, they change which genes a cell turns on or off. This process has uses in reproductive cloning for livestock propagation and in regenerative medicine, where patient-specific cells may help with injury repair. A key step in nuclear reprogramming is opening the DNA inside the nucleus so regulatory proteins can reach it. Cells...

cloning of dolly the sheep

How Dolly the Sheep Was Cloned

Dolly the sheep was the first successfully cloned mammal. She was born on 5 July 1996 at the Roslin Institute in Scotland, and her name came from the American singer Dolly Parton. Dolly lived for seven years, and she died from respiratory complications. Scientists think her shortened life may have been linked to the age of the DNA used to make her. In cloned cells, the DNA comes from an older individual. Analysis of Dolly’s DNA also showed shorter telomeres than those in other sheep of the...

key terms and concepts

Learn how nuclear reprogramming changes cell fate through epigenetic changes, SCNT, and Yamanaka factors that create induced pluripotent stem cells.

How Nuclear Reprogramming Changes Cell Fate | JoVE K12

cell biology

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How Nuclear Reprogramming Changes Cell Fate

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