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Related Concept Videos

Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Tissue Renewal without Stem Cells01:23

Tissue Renewal without Stem Cells

After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
However, failure of such a system...
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.
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the goblet,...

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Isolation of Regenerating Hepatocytes after Partial Hepatectomy in Mice
10:04

Isolation of Regenerating Hepatocytes after Partial Hepatectomy in Mice

Published on: December 2, 2022

Robust cellular reprogramming occurs spontaneously during liver regeneration.

Kilangsungla Yanger1, Yiwei Zong, Lara R Maggs

  • 1Department of Medicine, Gastroenterology Division.

Genes & Development
|March 23, 2013
PubMed
Summary

Cellular reprogramming in vivo is demonstrated by activating Notch signaling, which converts liver cells (hepatocytes) into bile duct cells (BECs). This process occurs naturally during liver injury and regeneration.

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Area of Science:

  • Regenerative Medicine
  • Cellular Biology
  • Developmental Biology

Background:

  • Cellular reprogramming, the conversion of one cell type to another, is key to regenerative medicine.
  • In vivo reprogramming without external factors is seldom observed, limiting therapeutic applications.
  • The Notch signaling pathway plays a crucial role in cell fate determination during liver development.

Purpose of the Study:

  • To investigate if Notch signaling activation can induce in vivo cellular reprogramming.
  • To determine if hepatocytes can be reprogrammed into biliary epithelial cells (BECs) via Notch signaling.
  • To explore the role of Notch-mediated reprogramming in liver regeneration following injury.

Main Methods:

  • Activation of the Notch signaling pathway in vivo.
  • Utilizing lineage tracing techniques to track cell fate changes.
  • Inducing liver injury models that trigger a biliary response.

Main Results:

  • Notch pathway activation is sufficient to reprogram hepatocytes into BECs in vivo.
  • Hepatocytes undergo significant reprogramming into BECs during liver injury and regeneration.
  • This hepatocyte-to-BEC reprogramming process is dependent on Notch signaling.

Conclusions:

  • In vivo cellular reprogramming can occur without exogenous factors, driven by intrinsic signaling pathways like Notch.
  • Mammalian liver regeneration involves substantial cell identity changes, specifically hepatocyte-to-BEC conversion.
  • Understanding Notch-mediated reprogramming offers new avenues for regenerative medicine therapies.