Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Intestinal health: Dresden research team identifies enzyme essential for stem cell survival

08.06.2020

Which pathways govern intestinal epithelial differentiation under constitutive conditions? Epithelial differentiation is largely controlled by the tissue-specific activity of transcription factors. Access to DNA is provided by accessible chromatin (euchromatin), while compacted heterochromatin limits access of transcription factors to DNA. Researchers at the TU Dresden Center for Regenerative Therapies (CRTD) have investigated the significance of the regulation of heterochromatin formation in the intestinal epithelium and published their findings in the renowned international scientific journal Gut.

Study results contribute to the understanding of intestinal regeneration and prevention of intestinal inflammation


Healthy (right) vs diseased (left) bowel: Extensive DNA damage (green) within the intestinal epithelium leads to inflammatory cell death and disrupts intestinal homeostasis

© CRTD

The intestinal epithelium is the inner layer of the intestinal wall, which separates host tissue from the intestinal microbiota. This layer of cells plays a crucial role in water, electrolyte and nutrient absorption, while limiting the entry of bacteria, viruses, fungi, toxins and antigens into host tissue to ensure intestinal homeostasis.

The diverse functions carried out by the intestinal epithelium are supported by multiple specialised intestinal epithelial cells, which are replaced every three to five days from a pool of intestinal stem cells. This makes the intestinal epithelium one of the most rapidly renewing tissues in adult mammals.

Which pathways govern intestinal epithelial differentiation under constitutive conditions? Epithelial differentiation is largely controlled by the tissue-specific activity of transcription factors. Access to DNA is provided by accessible chromatin (euchromatin), while compacted heterochromatin limits access of transcription factors to DNA.

Researchers at the TU Dresden Center for Regenerative Therapies (CRTD) have now investigated the significance of the regulation of heterochromatin formation in the intestinal epithelium and published their findings in the renowned international scientific journal Gut.

In their study, Prof. Sebastian Zeißig’s team demonstrated the essential role of the SETDB1 protein involved in heterochromatin formation during intestinal epithelial cells differentiation, and its importance in preventing inflammation.

The scientists observed in mice the consequences of the enzyme loss in the intestinal stem cells: Endogenous retroviruses, which represent a relevant part of the human genome, accumulate within a few days, which leads to DNA damage, inflammatory cell death, and loss of intestinal epithelial stem cells as well as of differentiated epithelial cells.

This limits the absorption of fluid and nutrients, causes intestinal inflammation and inevitably leads to death within a few days.

"Our study reveals a fundamental importance of SETDB1 and heterochromatin formation in the maintenance of epithelial genome stability and the control of intestinal homeostasis," explains Prof Sebastian Zeißig, CRTD research group leader and physician at the Medical Clinic I of the University Hospital Carl Gustav Carus Dresden. "It remains to be seen whether mutations in this gene can also contribute to intestinal inflammation in humans, for example, in inflammatory bowel diseases.”

The study was funded by TU Dresden / CRTD within the German Excellence Initiative and supported by the DRESDEN-concept Genome Center and the Electron and Light Microscopy Facilities of TU Dresden CMCB Technology Platform.

Wissenschaftliche Ansprechpartner:

Prof. Sebastian Zeißig
Email: sebastian.zeissig@tu-dresden.de

Originalpublikation:

GUT: “SETDB1 is required for intestinal epithelial differentiation and the prevention of intestinal inflammation”, authors: Lea Južnić, Kenneth Peuker, Anne Strigli, Mario Brosch, Alexander Herrmann, Robert Häsler, Michael Koch, Liz Matthiesen, Yvonne Zeißig, Britt-Sabina Löscher, Alexander Nuber, Gunnar Schotta, Volker Neumeister, Triantafyllos Chavakis, Thomas Kurth, Mathias Lesche, Andreas Dahl, Anne von Mässenhausen, Andreas Linkermann, Stefan Schreiber, Konrad Aden, Philip Rosenstiel, Andre Franke, Jochen Hampe, Sebastian Zeißig

Kim-Astrid Magister | Technische Universität Dresden
Further information:
http://www.tu-dresden.de

More articles from Life Sciences:

nachricht Protein linked to cancer acts as a viscous glue in cell division
08.07.2020 | Rensselaer Polytechnic Institute

nachricht Enzymes as double agents: new mechanism discovered in protein modification
08.07.2020 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Excitation of robust materials

Kiel physics team observed extremely fast electronic changes in real time in a special material class

In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

 
Latest News

On-chip spin-Hall nanograting for simultaneously detecting phase and polarization singularities

08.07.2020 | Physics and Astronomy

Engineers use electricity to clean up toxic water

08.07.2020 | Agricultural and Forestry Science

Atomic 'Swiss army knife' precisely measures materials for quantum computers

08.07.2020 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>