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

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 th at 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.


'"/>

Source:University of Pennsylvania School of Medicine


Related biology news :

1. Master gene controls healing of skin in fruit flies and mammals
2. Master genetic switch found for chronic pain
3. Master planners in brain may coordinate other areas roles in cognitive tasks
4. Master regulatory gene of epithelial stem cells identified
5. White blood cell waste disposal system plays critical regulatory role
6. Researchers rein in regulatory RNAs
7. OneWorld Health drug receives Orphan designation from U.S. and European regulatory agencies
8. New technique helps identify multiple DNA regulatory sites
9. Smoking damages key regulatory enzyme in the lung
10. Key brain regulatory gene shows evolution in humans
11. New methods offer insight into regulatory DNA
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/22/2016)... WASHINGTON , June 22, 2016 On ... highly-anticipated call to industry to share solutions for the ... by U.S. Customs and Border Protection (CBP), explains that ... nationals are departing the United States ... criminals, and to defeat imposters. Logo - ...
(Date:6/9/2016)... control systems is proud to announce the introduction of fingerprint attendance control software, allowing ... are actually signing in, and to even control the opening of doors. ... ... ... Photo - http://photos.prnewswire.com/prnh/20160609/377487 ...
(Date:6/2/2016)... , June 2, 2016   The Weather Company , ... Watson Ads, an industry-first capability in which consumers will be ... able to ask questions via voice or text and receive ... Marketers have long sought an advertising ... that can be personal, relevant and valuable; and can scale ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... -- Andrew D Zelenetz , ... Published recently in Oncology & ... Andrew D Zelenetz , discusses the fact ... placing an increasing burden on healthcare systems worldwide, ... the patents on many biologics expiring, interest in ...
(Date:6/23/2016)... ... June 23, 2016 , ... Velocity Products, a division ... tuned and optimized exclusively for Okuma CNC machining centers at The International Manufacturing ... collaboration among several companies with expertise in toolholding, cutting tools, machining dynamics and ...
(Date:6/22/2016)... DUBLIN , June 22, 2016 Research ... and Global Markets" report to their offering. ... $39.4 billion in 2014 from $29.3 billion in 2013. The market ... (CAGR) of 13.8% from 2015 to 2020, increasing from $50.6 billion ... and projected product forecasts during the forecast period (2015 to 2020) ...
(Date:6/22/2016)... , June 22, 2016   ViaCyte, Inc. , ... stem cell-derived islet replacement therapy for the treatment of ... ISSCR 2016 Annual Meeting.  ISSCR 2016, the Global Stem ... at Moscone West in San Francisco.  ... presentations are as follows:Event: , Focus Session: Tools for ...
Breaking Biology Technology: