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:6/30/2017)... June 30, 2017 Today, American Trucking ... supplier of face and eye tracking software, became ... provider program. "Artificial intelligence and ... to monitor a driver,s attentiveness levels while on ... able to detect fatigue and prevent potential accidents, ...
(Date:5/16/2017)...  Veratad Technologies, LLC ( www.veratad.com ), an innovative ... verification solutions, announced today they will participate as a ... thru May 17, 2017, in Washington D.C.,s ... Identity impacts the lives of billions ... evolving digital world, defining identity is critical to nearly ...
(Date:4/19/2017)... The global military biometrics market ... by the presence of several large global players. The ... major players - 3M Cogent, NEC Corporation, M2SYS Technology, ... 61% of the global military biometric market in 2016. ... military biometrics market boast global presence, which has catapulted ...
Breaking Biology News(10 mins):
(Date:9/12/2017)... New Brunswick, NJ (PRWEB) , ... September 12, ... ... as one of the fastest growing b2b product testing and development companies will ... their expanded service offerings. , Contract Pharma is an ...
(Date:9/12/2017)... ... September 12, 2017 , ... It wasn’t just the San Diego temps that ... hot, as Lajollacooks4u has had a record-breaking number of guests for corporate cooking challenges, ... wide to celebrate company outings, family get-togethers, anniversaries and milestone birthdays. While all ...
(Date:9/12/2017)... ... September 12, 2017 , ... September 15, 2017. ... Nicholson, Head of the Department of Surgery and Cancer and Director of the ... Coulter Lecture. His presentation, “Analytical Science in Precision Medicine: Facing the Challenges ...
(Date:9/12/2017)... Wayne, PA (PRWEB) , ... September 12, 2017 , ... ... and growing life sciences teams, today announced that Tobias Massa, PhD has joined the ... pharmaceuticals, biotech, life sciences, and technology to his Board position. Most recently he served ...
Breaking Biology Technology: