Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Master regulatory gene found that guides fate of blood-producing stem cells

02.08.2005


Discovery may lead to new therapies for leukemia, other blood disorders



Researchers from the University of Pennsylvania School of Medicine found that a protein called NF-Ya activates several genes known to regulate the development of hematopoietic stem cells (HSC), or blood-producing stem cells, in bone marrow. Knowing the details of this pathway may one day lead to new treatments for such blood diseases as leukemia, as well as a better understanding of how HSCs work in the context of bone-marrow and peripheral-stem-cell transplantation. The authors published their findings in the early August issue of the Proceedings of the National Academy of Sciences.

"Understanding the biology behind how the body precisely controls stem-cell fate is one of the most important issues in stem-cell biology," says senior author Stephen G. Emerson, MD, PhD, Associate Director of Clinical Research for Penn’s Abramson Cancer Center and Chief of the Division of Hematology-Oncology. When HSCs divide, they have one of three fates: develop into two more stem cells, which is called self-renewal; differentiate to become one of several mature blood-cell types; or strike a balance in which one daughter cell becomes an HSC and the other becomes a mature blood-cell type.


"We know that in diseases like leukemia, the first scenario-no differentiated cells, two HCSs developing-must occur because more and more stem cells are made," explains Emerson. In conditions like bone-marrow failure, the second scenario-two differentiated cells and no HCSs-happens because the body runs out of HSCs.

"We want to figure out how this process is normally regulated in the body, so that we can learn to control it for therapeutic purposes," says Emerson. "For some clinical purposes, we might want to shift the balance so that we can grow more stem cells, for those who need them. Conversely, for patients in whom this process has gone awry, such as acute leukemia, we might block the regulatory gene to shift the balance of self-renewal versus differentiation so that all the immature, leukemic cells differentiate and die.

Over the past 10 years, several gene families have been suggested to be important in regulating HSC fate-for example homebox, wnt, notch 1, and telomerase genes. Emerson and colleagues figured that one transcription factor, called NF-Y, was required for activating promoters of all of these genes. What’s more, they found that fully assembled NF-Y was activated in stem cells and disappeared when the stem cells became mature cell types, through the induction and loss of one its subunits, NF-Ya.

"When we overexpressed NF-Ya in stem cells, the stem cells produced ten- to twenty-fold more stem cells after transplantation," says Emerson. "This makes NF-Ya the prime candidate for a master-regulatory gene for multiple, if not all, stem-cell division programs." NF-Ya would be considered the master regulatory gene since it activates multiple HSC regulatory genes and promotes HSC self-renewal.

Practically, the researchers’ goal is to find a way to control stem-cell fate by biochemically turning NF-Ya on or off at will, to either make more stem cells in the case of bone-marrow failure and for transplantation, or to force the cells to differentiate, in the case of leukemia, where too many HSCs are made.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu/news.

More articles from Life Sciences:

nachricht Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>