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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Lineage Commitment01:21

Lineage Commitment

Commitment is the  process whereby stem cells:
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
Multipotency of Hematopoietic Stem Cells01:19

Multipotency of Hematopoietic Stem Cells

The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...

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Related Experiment Video

Updated: Jun 14, 2026

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
05:48

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

Published on: January 2, 2018

O-fucose modulates Notch-controlled blood lineage commitment.

Quanjian Yan1, David Yao, Lebing L Wei

  • 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.

The American Journal of Pathology
|April 6, 2010
PubMed
Summary

Cellular fucosylation, regulated by Pofut1, is crucial for Notch signaling in hematopoietic stem cells. Loss of fucosylation impairs lymphoid development and promotes myeloid cell growth, disrupting blood cell balance.

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Combining Intravital Fluorescent Microscopy (IVFM) with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches
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Combining Intravital Fluorescent Microscopy (IVFM) with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches

Published on: March 21, 2017

Related Experiment Videos

Last Updated: Jun 14, 2026

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
05:48

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

Published on: January 2, 2018

Combining Intravital Fluorescent Microscopy (IVFM) with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches
11:06

Combining Intravital Fluorescent Microscopy (IVFM) with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches

Published on: March 21, 2017

Area of Science:

  • Cellular biology
  • Hematopoiesis
  • Molecular signaling

Background:

  • Notch receptors are key regulators of cell fate determination.
  • O-linked fucosylation, catalyzed by Pofut1, is a critical posttranslational modification of Notch receptors.
  • Previous studies linked cellular fucosylation deficiency to myeloproliferation due to impaired Notch-dependent myelopoiesis suppression.

Purpose of the Study:

  • To investigate the role of cellular fucosylation in hematopoietic stem cell (HSC) function and lineage potential.
  • To elucidate the impact of impaired Notch signaling, due to fucosylation deficiency, on lymphoid and myeloid development.
  • To determine the necessity of Notch1 and Pofut1 for maintaining hematopoietic lineage homeostasis.

Main Methods:

  • Analysis of HSC frequency, repopulating ability, and developmental potential in fucosylation-deficient mice.
  • In vitro coculturing of Notch1 or Pofut1 deficient embryonic stem cells with Notch ligand-expressing bone marrow stromal cells.
  • In vivo hematopoietic reconstitution assays using CD34+ progenitor cells from Notch1 or Pofut1 deficient embryonic stem cells.

Main Results:

  • Hematopoietic stem cells deficient in cellular fucosylation showed reduced frequency, impaired repopulating ability, decreased lymphoid, and increased myeloid developmental potential.
  • Deficiency in Notch1 or Pofut1 in embryonic stem cells resulted in failure to generate T lymphocytes and a bias towards myeloid differentiation.
  • In vivo reconstitution experiments confirmed enhanced granulopoiesis and depressed lymphoid lineage development in Notch1 or Pofut1 deficient progenitor cells.

Conclusions:

  • Notch signaling, modulated by O-linked fucosylation, is essential for maintaining hematopoietic lineage homeostasis.
  • Proper fucosylation of Notch receptors promotes lymphoid development and suppresses excessive myelopoiesis.
  • Disruption of Notch receptor fucosylation leads to aberrant hematopoiesis with a bias towards myeloid lineages.