Related Experiment Video
Updated: Dec 2, 2025
06:40
3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation
Published on: April 1, 2021
5.2K
Mitochondria Define Intestinal Stem Cell Differentiation Downstream of a FOXO/Notch Axis
Marlies C Ludikhuize1, Maaike Meerlo1, Marc Pages Gallego1
1Molecular Cancer Research, Center Molecular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CG Utrecht, the Netherlands.
Cell Metabolism
|November 4, 2020
Summary
Forkhead box O (FoxO) and Notch signaling regulate intestinal stem cell differentiation by controlling mitochondrial activity. This discovery reveals a novel signaling-metabolic pathway crucial for cell fate determination.
Area of Science:
- Cell Biology
- Developmental Biology
- Metabolism
Background:
- WNT and Notch signaling pathways control intestinal stem cell differentiation.
- Mitochondrial activity differs between intestinal stem cells and differentiated Paneth cells, suggesting a metabolic shift during differentiation.
Purpose of the Study:
- To investigate the interaction between Forkhead box O (FoxO) transcription factors, Notch signaling, and mitochondrial activity in regulating Lgr5+ crypt-based columnar cell (CBC) differentiation.
- To elucidate the role of mitochondria in the metabolic transition during CBC differentiation into secretory lineages.
Main Methods:
- Organoid culture and mouse intestinal models.
- Deletion of Foxo1/3/4 genes.
- Single-cell RNA sequencing (scRNA-seq) to reconstruct differentiation trajectories.
Main Results:
- FoxO transcription factors and Notch signaling interact to determine CBC fate.
- Deletion of Foxo1/3/4 in mice promotes secretory cell differentiation.
- FOXO and Notch signaling converge on regulating mitochondrial fission, driving stem cell differentiation into goblet cells and Paneth cells.
- scRNA-seq data supports the involvement of FOXO, Notch, and mitochondria in secretory differentiation.
Conclusions:
- A novel signaling-metabolic axis involving FOXO, Notch, and mitochondria regulates intestinal stem cell differentiation.
- Mitochondrial dynamics play a critical role in determining stem cell fate and lineage commitment.
Related Concept Videos
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.3K
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...
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...
2.3K
01:23Renewal of Intestinal Stem Cells
3.0K
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...
3.0K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.5K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.5K
01:26Stem Cell Niche
5.9K
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
5.9K
01:33Adult Stem Cells
32.2K
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...
32.2K
00:57Cellular Differentiation
4.6K
How does a complex organism such as a human develop from a single cell? It all starts from a single fertilized egg which gives rise to a vast array of cell types, such as nerve cells, muscle cells, and epithelial cells that characterize the adult? Throughout development and adulthood, cellular differentiation leads cells to assume their final morphology and physiology. Differentiation is the process by which unspecialized cells become specialized to carry out distinct functions.
A zygote is a...
A zygote is a...
4.6K