Related Experiment Video

Updated: Apr 17, 2026

3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation
06:40

3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation

Published on: April 1, 2021

5.5K

HDAC1 and HDAC2 collectively regulate intestinal stem cell homeostasis

Cheryl D Zimberlin1, Cesare Lancini1, Rachel Sno1

  • 1*Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands; Tygat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; and Cancer Genomics Center, Utrecht, The Netherlands.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|February 5, 2015
PubMed

Insights

Histone deacetylases 1 and 2 (HDAC1 and HDAC2) are vital for maintaining intestinal homeostasis. Their simultaneous deletion causes rapid loss of gut lining integrity, highlighting their essential, redundant roles.

Area of Science:

  • Cell Biology
  • Gastroenterology
  • Epigenetics

Background:

  • Histone deacetylases (HDACs) regulate gene expression through protein deacetylation.
  • Broad-spectrum HDAC inhibitors (HDACi) show clinical efficacy but cause side effects.
  • Understanding specific HDAC functions is crucial for targeted therapies.

Purpose of the Study:

  • To investigate the role of HDAC1 and HDAC2 in intestinal homeostasis.
  • To determine the consequences of simultaneous HDAC1 and HDAC2 deletion in adult mouse intestine.
  • To explore the impact of HDAC1/HDAC2 loss on intestinal stem cells.

Main Methods:

  • Generation of a novel mouse model for inducible, simultaneous deletion of HDAC1 and HDAC2 in the adult intestine.
  • In vitro studies using intestinal organoid cultures.
  • Treatment of organoids with a class I-specific HDAC inhibitor (MS-275).

Main Results:

  • Simultaneous deletion of HDAC1 and HDAC2 rapidly disrupted intestinal homeostasis.
  • Intestinal lining was repopulated by surviving stem cells within 8 days.
  • In vitro ablation of HDAC1/HDAC2 and MS-275 treatment reduced stem cell markers and clonogenic capacity.

Conclusions:

  • HDAC1 and HDAC2 possess redundant functions and are essential for maintaining intestinal homeostasis.
  • Loss of HDAC1/HDAC2 function impairs intestinal stem cell function and stemness.
  • Findings provide a potential explanation for gastrointestinal side effects of HDAC inhibitors.
Keywords:
MS-275histone deacetylasehistone deacetylase inhibitororganoids

More Related Videos

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation09:10

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation

Published on: July 27, 2022

2.8K
Generation, Maintenance, and Characterization of Human Pluripotent Stem Cell-derived Intestinal and Colonic Organoids08:13

Generation, Maintenance, and Characterization of Human Pluripotent Stem Cell-derived Intestinal and Colonic Organoids

Published on: July 9, 2021

2.9K

Related Concept Videos

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...
2.6K
Renewal of Intestinal Stem Cells01:23

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...
3.7K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

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.
2.8K
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...
4.5K
Adult Stem Cells01:33

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...
34.5K
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...
4.2K