Navigation Links
Caltech biologists discover microRNAs that control function of blood stem cells
Date:8/4/2010

PASADENA, Calif.Hematopoietic stem cells provide the body with a constant supply of blood cells, including the red blood cells that deliver oxygen and the white blood cells that make up the immune system. Hematopoieticor bloodstem cells must also make more copies of themselves to ensure that they are present in adequate numbers to provide blood throughout a person's lifetime, which means they need to strike a delicate balance between self-renewal and development into mature blood-cell lineages. Perturb that balance, and the result can be diseases such as leukemia and anemia.

One key to fighting these diseases is gaining an understanding of the genes and molecules that control the function of these stem cells. Biologists at the California Institute of Technology (Caltech) have taken a large step toward that end, with the discovery of a novel group of molecules that are found in high concentrations within hematopoietic stem cells and appear to regulate their production.

When the molecules, tiny snippets of RNA known as microRNAs (miRNAs), are experimentally elevated to higher levels in the hematopoietic stem cells of laboratory mice, they "either impede or accelerate the function of these cells," says David Baltimore, Robert Andrews Millikan Professor of Biology, recipient of the 1975 Nobel Prize in Physiology or Medicine, and principal investigator on the research.

A paper about the work was published July 26 in the early online edition of the Proceedings of the National Academy of Sciences (PNAS).

Intriguingly, the researchers found that one particular miRNA, miR-125b, plays a striking dual role. When miR-125b was mildly elevated, it accelerated the production of mature blood cells by blood stem cells far better than any other miRNA. But when its expression was pushed to far higher levels, Baltimore says, "it led to a vicious cancer within 6 months." While the exact mechanism underlying this transformation event is presently unknown, it likely involves the inhibition by miR-125b of specific genes that normally suppress tumor formation.

"We were surprised to see that at high levels, miR-125b induced an aggressive myeloid leukemia in mice," says Caltech graduate student Aadel Chaudhuri, a coauthor on the paper. Myeloid leukemia results when normal blood cellsincluding red blood cells, blood-clotting platelets, and white blood cellsare systematically replaced by abnormal white blood cells that continue to grow uncontrollably, ultimately leading to death if untreated.

"These studies were performed in mice," says Caltech postdoctoral scholar Ryan O'Connell, the lead author of the PNAS paper, "but we also analyzed human blood stem cells and found that the same miRNAs are similarly enriched."

In addition, the researchers found that the expression of that key miRNA enhances the engraftment of human blood stem cells when they are transferred into mouse hosts, "indicating that the expression and function of these miRNAs has been conserved during evolution," O'Connell says.

That means, Chaudhuri says, "it is possible that certain human leukemias could be treated by targeting these newly identified stem-cell microRNAs."

"These findings, when combined with a similar report by physicianscientist David Scadden of the Massachusetts General Hospital and the Harvard Stem Cell Institute, show that miRNAs are important molecules that control the function of blood stem cells," he says. "These observations have important implications for both the diagnosis and treatment of cancer and anemia, which arise from defective blood stem cells. Blood stem cell transplantations have become a common form of therapy to treat cancer, autoimmunity, and even certain types of infectious diseases, and the exploitation of miRNA expression levels in blood stem cells through therapeutic targeting could be used to augment this approach."

"These two studies add to the mounting evidence that miRNAs are critical controllers of the relative amounts of different types of blood cells made in the bone marrow of mice and people," Baltimore says. "In this work, we show that this is true for the stem cells, while earlier work from us and many others has shown that miRNA levels determine the concentrations of many types of mature blood cells. This knowledge offers the opportunity to therapeutically manipulate the levels of these blood cells," he says, "although targeting miRNAs therapeutically remains a great challenge to biotechnology."


'/>"/>

Contact: Kathy Svitil
ksvitil@caltech.edu
626-395-8022
California Institute of Technology
Source:Eurekalert

Related medicine news :

1. Caltech scientists uncover structure of key protein in common HIV subgroup
2. Physicists help biologists to understand protein folding
3. U. Iowa biologists publish findings on cell interactions
4. Researchers discover new way to kill pediatric brain tumors
5. Scientists Discover How HIV Is Transmitted Between Men
6. First Gene Variants Linked to Stuttering Discovered
7. Researchers Who Discovered First Genes for Stuttering will Present Findings to the National Stuttering Association
8. Scientists Discover Molecular Pathway for Organ Tissue Regeneration and Repair
9. IU research team discovers TB disease mechanism and molecule to block it
10. Researchers discover second protective role for tumor-suppressor
11. UCSF Enters Drug Discovery Agreement with Genentech
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/21/2017)... ... 21, 2017 , ... The Visiting Nurse Association of ... R. Bard Foundation, Inc. to support the music therapy program offered at ... the nonprofit home care agency. Using evidence-based methods, professionally trained and certified music ...
(Date:7/21/2017)... ... July 21, 2017 , ... Sharon Kleyne is ... product of her research center at Bio-Logic Aqua Research® Water Life Science®, has ... greatest number of sufferers of blindness. “We think that Nature’s Tears® EyeMist® will ...
(Date:7/21/2017)... ... July 21, 2017 , ... The most common ... improved quality of life five years after injury, according to research presented today ... Toronto, Ontario, Canada. The study followed patients for five years following surgery. , ...
(Date:7/20/2017)... ... , ... ChenMed , a leading provider of value-based care for seniors, ... as Richmond Chief Medical Officer. Dr. McCarter, formerly Associate Professor of Family Medicine ... Ambulatory Services for the UVA Health System, brings 30 years of highly relevant experience ...
(Date:7/20/2017)... ... July 20, 2017 , ... ... Houston, is pleased to announce their expansion to the Midwest with the establishment ... Alysse Hollis and Ronald Bell, and of counsels, John Peck and Robert Bruns, ...
Breaking Medicine News(10 mins):
(Date:7/10/2017)... July 10, 2017  US medical equipment and supply ... according to Medical Equipment & Supplies: United ... Focus Reports. Continued increases in demand for medical services ... the population and supported by gains in disposable personal ... supplies. New product introductions will also drive sales as ...
(Date:7/6/2017)... ThriveRx, the nutrition division of Diplomat Specialty Infusion Group, is ... nutrition support. To celebrate its anniversary, ThriveRx recently launched a ... new look with improved organization to create the best user experience for ... ... "We,ve made several great strides ...
(Date:7/1/2017)... 30, 2017 Zimmer Biomet Holdings, Inc. (NYSE and ... conference call will be broadcast live over the Internet on ... news release detailing the quarterly results will be made available ... call. The live audio webcast can be accessed ... It will be archived for replay following the conference call. ...
Breaking Medicine Technology: