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Related Concept Videos

Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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General Transcription Factors01:30

General Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Determination01:51

Determination

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During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
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Related Experiment Video

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The GLI code controls HNF1A levels during foregut differentiation.

Lucas Unger1, Andreas F Mathisen1, Simona Chera1

  • 1Mohn Research Center for Diabetes Precision Medicine, Department of Clinical Science, Faculty of Medicine, University of Bergen, Norway.

The International Journal of Developmental Biology
|January 25, 2024
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Summary

Inhibiting Hedgehog signaling is crucial for pancreatic islet cell regeneration. This study shows that blocking Hedgehog targets via GLI3-R is necessary for efficient HNF1A expression, a key factor in endocrine cell development.

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Area of Science:

  • Stem cell biology
  • Developmental biology
  • Endocrinology

Background:

  • Human induced pluripotent stem cells (hiPSCs) differentiation into pancreatic islet endocrine cells is complex.
  • Key developmental pathways, including Hedgehog (HH) signaling, require modulation during differentiation.
  • Transcription factors like HNF1A are critical for islet endocrine cell fate, with specific expression changes observed.

Purpose of the Study:

  • To investigate the interconnection between HH signaling inhibition and increased HNF1A expression during early pancreatic regeneration.
  • To explore the role of GLI code modulation in this process.

Main Methods:

  • Pilot study involving hiPSC differentiation.
  • Modulation of Hedgehog signaling pathway activity.
  • Analysis of GLI code and HNF1A expression patterns.

Main Results:

  • A link was identified between HH signaling inhibition and HNF1A expression.
  • GLI3-R mediated inhibition of HH target genes appears essential for efficient HNF1A expression.
  • This suggests a regulatory mechanism involving GLI3-R in pancreatic endocrine cell fate determination.

Conclusions:

  • HH signaling inhibition, specifically through GLI3-R, is a critical requirement for the efficient expression of HNF1A during pancreatic islet endocrine cell differentiation.
  • Understanding this pathway provides insights into improving regenerative strategies for diabetes treatment.