Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find mechanism that may determine early blood cell fate

15.07.2003


Remain a hematopoetic stem cell or become a specialized blood cell?



Hematopoietic stem cells, the mother of all blood cells, face a fundamental dilemma in their lives.

Each must either remain a hematopoietic stem cell (HSC) by renewing itself or it must transform into one of eight specialized types of blood cells, such as a red blood cell, a white blood cell or a platelet.


Until recently, scientists didn’t know how the essential cells, which exist in limited amounts in the body, decide which direction to go. Now, researchers in the University of Wisconsin Medical School Department of Pharmacology have found a mechanism that might determine what each HSC will be. The mechanism involves an unexpected interaction between two related proteins.

Appearing in the July 11, 2003 issue of the Proceedings of the National Academy of Sciences (online), the study should be of special interest to hematologists treating patients with severe cancer, which can deplete blood cells, or blood disorders such as sickle cell disease, beta thalassemia or alpha thalassemia. One common treatment has been to introduce HSCs into the body, where they produce new blood cells to counteract abnormal blood cells or replace absent blood cells.

In the recent past, most blood specialists extracted HSC from bone marrow, where the cells occur in relatively large numbers; however, the procedure can be difficult on some patients. Today, a growing number of hematologists are extracting HSC much more easily from peripheral blood or umbilical cord blood. But since fewer cells are present in these sources, it would be advantageous to expand the cells to increase their numbers, explained Emery Bresnick, UW Medical School professor of pharmacology and senior author on the study.

"Manipulations to expand stem cell numbers can cause the cells to lose their ability to remain stem cells," Bresnick said. "Any mechanism that tells you how to maintain stem cell status and prevent differentiation is a good target for modulating and improving this whole process. We discovered a mechanism that is an excellent candidate for controlling the decision of whether the HSC should remain undifferentiated or form blood."

Bresnick and researchers Jeffrey Grass, Meghan Boyer, Soumen Paul and Jing Wu focused on two members of the GATA family of proteins, which are known to play a central role in the development of blood cells. GATA proteins work by attaching to portions of target genes, which either starts or stops the gene activity.

The researchers zeroed in first on GATA-2, which is required in significant levels for HSC to differentiate into intermediate blood cells called multi-potent progenitor cells. But the protein levels must go down before the progenitor cells can undergo further differentiation into distinct blood cell types.

"A central unsolved question was what signals tell the GATA-2 gene to stop producing its proteins so the progenitor cells can form blood," Bresnick said.

To find the answer, he and his team also examined GATA-1. Significant amounts of this protein are critical for the formation of several types of blood cells: red cells, which carry hemoglobin to the lungs; mast cells, which mediate important aspects of immunity and asthma; and platelets, which are needed for blood clotting. However, GATA-1 levels must be lowered if HSCs are to be sustained in an undifferentiated state.

"We reasoned that there was a reciprocal, opposing relationship between GATA-1 and GATA-2," Bresnick said.

By observing the way the proteins interact with sequences of genes in living cells, Bresnick and his colleagues found a master region on the GATA-2 gene that regulates the relationship. They found that when the GATA-2 gene is active, GATA-2 proteins attach to the region; when the GATA-2 gene is inactive, GATA-1 proteins attach to the region. As GATA-1 levels increase, the protein attaches to the region, signaling the GATA-2 gene to stop making GATA-2 protein.

The net effect, said Bresnick, is that if GATA-1 is occupying the master region, the gene activity stops, and the cell will differentiate. On the other hand, if GATA-2 binds to the region, gene activity begins, preventing differentiation and supporting stem cell function.

"It’s a delicate balance between two highly related proteins, but if we can shift the balance by modulating this relationship, we can chose to increase the number of these limited HSC or stimulate hematopoisis," Bresnick said.

Dian Land | EurekAlert!
Further information:
http://www.wisc.edu/

More articles from Life Sciences:

nachricht Zeolite catalysts pave the road to decentral chemical processes Confined space increases reactivity
28.06.2017 | Technische Universität München

nachricht For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Extensive Funding for Research on Chromatin, Adrenal Gland, and Cancer Therapy

28.06.2017 | Awards Funding

Predicting eruptions using satellites and math

28.06.2017 | Earth Sciences

Extremely fine measurements of motion in orbiting supermassive black holes

28.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>