Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein found to regulate red blood cell size and number

29.08.2012
The adult human circulatory system contains between 20 and 30 trillion red blood cells (RBCs), the precise size and number of which can vary from person to person.

Some people may have fewer, but larger RBCs, while others may have a larger number of smaller RBCs. Although these differences in size and number may seem inconsequential, they raise an important question: Just what controls these characteristics of RBCs?

This question is particularly relevant for the roughly one-quarter of the population that suffers from anemia, which is often caused by flawed RBC production. A better understanding of how RBC production is controlled may offer greater insight into the development and potential treatment of anemia.

By analyzing the results of genome-wide association studies (GWAS) in conjunction with experiments on mouse and human red blood cells, researchers in the lab of Whitehead Institute Founding Member Harvey Lodish have identified the protein cyclin D3 as regulating the number of cell divisions RBC progenitors undergo, which ultimately affects the resulting size and quantity of RBCs. Their findings are reported in the September 14 issue of Genes and Development.

"This is one of the rare cases where we can explain a normal human-to-human variation," says Lodish, who is also a professor of biology and bioengineering at MIT. "In a sense, it's a window on human evolution. Why this should have happened, we have no idea, but it does."

Lodish likens cyclin D3's role in RBCs to that of a clock. In some people, the clock triggers RBC progenitors to mature after four rounds of cell division, resulting in fewer but larger RBCs. In others it goes off after five cell division cycles, which leads to production of a greater number of smaller RBCs. In both cases, the blood usually has the same ability to carry oxygen to distant tissues.

The initial hint of cyclin D3's importance came from GWAS, genetic surveys of large numbers of people with or without a particular trait. Researchers compare the groups in an attempt to identify genetic variations.

"The problem with most GWAS is that you get a bunch of potentially interesting genes, but that doesn't tell you anything about the functional biology, so you really have to figure it out," says Leif Ludwig, a Lodish graduate student and co-author of the Genes and Development paper. "You only know something has a role, but you don't know how it can cause variation. This work on cyclin D3 is a really nice example of how functional follow-up on a GWAS association can really teach us something about underlying biology."

In the case of RBC size and number, a mutation affecting cyclin D3 production bubbled to the surface from the GWAS's murky genetic data. Ludwig and co-author Vijay Sankaran then confirmed that reduced or inhibited cyclin D3 expression in mice and in human RBC progenitors caused those cells to halt cell division and mature earlier, producing larger and fewer red blood cells than mice and cells with uninhibited cyclin D3 production.

As one of only a handful of studies that have successfully used GWAS to produce definitive biological results, Sankaran is excited that this work confirms the value of such genetic studies.

"Can genetics teach us about biology?" asks Sankaran, also a postdoctoral researcher in the Lodish lab. "Yes! This work tells us that as genetic studies identify new genes, there will probably have been a lot of things biologists may have ignored. Genetics allows you to shine a spotlight on something interesting and then home in on it see what can be learned."

This work was supported by the National Institutes of Health (NIH), Boehringer Ingelheim Fonds, and Amgen, Inc.

Written by Nicole Giese Rura

Harvey Lodish's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology and a professor of bioengineering at Massachusetts Institute of Technology.

Full Citation:

"Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number"

Genes and Development, XXXXXX XX, 2012.

Vijay G. Sankaran (1,2,3,8,†), Leif S. Ludwig (2,14,†), Ewa Sicinska (5,*), Jian Xu (4,6,*), Daniel E. Bauer (4,6,*), Jennifer C. Eng (1,2), Heide Christine Patterson (2,12), Ryan A. Metcalf (13), Yasodha Natkunam (13), Stuart H. Orkin (1,4,6,8), Piotr Sicinski (7,9), Eric S. Lander (1,10,11,ǂ), and Harvey F. Lodish (1,2,11,ǂ)

1. Broad Institute, Cambridge, Massachusetts, USA.

2. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.

3. Department of Medicine Children's Hospital Boston, Boston, Massachusetts, USA.

4. Division of Hematology/Oncology, Children's Hospital Boston, Boston, Massachusetts, USA.

5. Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

6. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

7. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

8. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

9. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
10. Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.

11. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

12. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

13. Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

14. Institute for Chemistry and Biochemistry, Freie Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany.

†These authors contributed equally to this work.

*These authors contributed equally to this work.

ǂThese authors jointly directed this work.

Nicole Rura | EurekAlert!
Further information:
http://www.wi.mit.edu

More articles from Life Sciences:

nachricht Bacteria as pacemaker for the intestine
22.11.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Corporate coworking as a driver of innovation

22.11.2017 | Business and Finance

PPPL scientists deliver new high-resolution diagnostic to national laser facility

22.11.2017 | Physics and Astronomy

Quantum optics allows us to abandon expensive lasers in spectroscopy

22.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>