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Related Concept Videos

Cell Specific Gene Expression01:58

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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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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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The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
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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.
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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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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Related Experiment Video

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Small Molecules Facilitate Single Factor-Mediated Hepatic Reprogramming.

Kyung Tae Lim1, Seung Chan Lee2, Yimeng Gao3

  • 1Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea.

Cell Reports
|May 7, 2016
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Summary
This summary is machine-generated.

Researchers discovered a stepwise process for converting fibroblasts into induced hepatocyte-like cells (iHeps). Adding c-Myc and Klf4 (CK) factors significantly boosted efficiency, and small molecules enabled robust iHep generation, paving the way for clinical applications.

Keywords:
METconversion kineticsdirect conversioninduced hepatocytes

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In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
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Area of Science:

  • Cellular reprogramming and regenerative medicine
  • Hepatocyte differentiation and liver disease modeling

Background:

  • Direct conversion of fibroblasts to induced hepatocyte-like cells (iHeps) is promising but limited by low efficiency and unknown mechanisms.
  • Understanding the stepwise process of hepatic reprogramming is crucial for improving cell generation.

Purpose of the Study:

  • To elucidate the underlying mechanism of direct hepatic reprogramming.
  • To identify factors and small molecules that enhance the efficiency and robustness of iHep generation.

Main Methods:

  • Investigated the stepwise transition during direct conversion, including somatic memory erasure, mesenchymal-to-epithelial transition, and hepatic fate induction.
  • Screened for factors enhancing conversion kinetics, identifying c-Myc and Klf4 (CK).
  • Identified small molecules for robust iHep generation, with and without CK, and tested Hnf1α in combination with small molecules.

Main Results:

  • Direct hepatic reprogramming proceeds through sequential steps: somatic memory erasure, mesenchymal-to-epithelial transition, and hepatic cell fate induction.
  • Co-expression of c-Myc and Klf4 (CK) significantly accelerated conversion kinetics and improved iHep generation efficiency.
  • Small molecules alone were identified to robustly generate iHeps, and Hnf1α combined with small molecules proved sufficient for efficient direct hepatic reprogramming.

Conclusions:

  • Direct conversion to iHeps is a stepwise process that can be significantly enhanced by specific factors (CK) and small molecules.
  • The findings provide a mechanistic understanding of direct hepatic reprogramming and offer a robust method for iHep generation.
  • This optimized approach holds potential for advancing the clinical translation of iHeps for liver disease therapies.