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 Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus 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: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>