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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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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.
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...
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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
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Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
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Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
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Related Experiment Video

Updated: Feb 8, 2026

Enumeration of Neural Stem Cells Using Clonal Assays
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Time-resolved transcriptomics in neural stem cells identifies a v-ATPase/Notch regulatory loop.

Sebastian Wissel1, Heike Harzer1, François Bonnay1

  • 1Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.

The Journal of Cell Biology
|July 1, 2018
PubMed
Summary

This study reveals vacuolar-type H+-ATPase (v-ATPase) downregulation is an early event in differentiating Drosophila neural stem cells. This impacts cell growth and Notch signaling, suggesting a regulatory loop crucial for stem cell fate.

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Area of Science:

  • Developmental Biology
  • Cell Biology
  • Genomics

Background:

  • Asymmetric cell division in Drosophila neural stem cells (NSCs) establishes distinct daughter cell fates.
  • While protein segregation mechanisms are known, the reprogramming events driving terminal differentiation remain unclear.

Purpose of the Study:

  • To identify early transcriptional differences between daughter cells with distinct fates.
  • To investigate the role of specific protein complexes in cell fate determination.

Main Methods:

  • Time-resolved transcriptional profiling of differentiating daughter cells.
  • Screening for coregulated protein complexes.
  • Functional assays to assess v-ATPase and Notch pathway roles.

Main Results:

  • Vacuolar-type H+-ATPase (v-ATPase) was identified as significantly downregulated in differentiating cells.
  • v-ATPase is essential for neural stem cell growth and Notch signaling pathway activity.
  • A regulatory loop between v-ATPase and Notch signaling was proposed.

Conclusions:

  • Transcriptional downregulation of v-ATPase is an early event in neural stem cell differentiation.
  • The v-ATPase and Notch signaling loop is critical for stem cell lineage progression in nervous system development and adult gut.
  • Cell fate changes can be regulated by fundamental cellular pathways.