Related Experiment Video
Updated: May 12, 2026

05:44
Monitoring Circadian Oscillations with a Bioluminescence Reporter in Organoids
Published on: February 16, 2024
The circadian clock gates the intestinal stem cell regenerative state
Phillip Karpowicz1, Yong Zhang, John B Hogenesch
1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. pkarpowicz@genetics.med.harvard.edu
Cell Reports
|April 16, 2013
Summary
The intestine
Area of Science:
- Gastroenterology
- Cell Biology
- Chronobiology
Background:
- Intestinal stem cells (ISCs) regenerate the intestine following damage.
- Key signaling pathways like Wnt, Notch, and Hippo regulate mammalian ISCs and are conserved across species.
Purpose of the Study:
- To investigate the role of the circadian clock in intestinal regeneration.
- To identify clock-regulated genes involved in the healing process.
Main Methods:
- Analysis of gene expression during intestinal regeneration.
- Investigating the impact of circadian clock disruption on ISC proliferation.
Main Results:
- The transcription factor period, a circadian clock component, is crucial for intestinal regeneration.
- Hundreds of transcripts, including stress response and regeneration pathway components, are clock-regulated during healing.
- Disruption of clock components results in arrhythmic ISC divisions.
Conclusions:
- The circadian clock plays a critical, underappreciated role in intestinal stem cell-mediated regeneration.
- Clock components regulate ISC division timing and contribute to the healing process.
Related Concept Videos
Renewal of Intestinal Stem Cells
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 goblet,...
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...
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...
Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
Adult Stem Cells
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 renew...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
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.

