Mystery solved: How thyroid hormone prods red blood cell productionSeptember 05, 2017
CAMBRIDGE, Mass. (September 5, 2017) - For more than a century, physicians have anecdotally noted that patients with an underactive thyroid--often caused by iodine deficiency--tended to also have anemia. But the link between thyroid hormone and red blood cell production has remained elusive. That is, until two postdoctoral researchers in the lab of Whitehead Institute Founding Member Harvey Lodish, Xiaofei Gao and Hsiang-Ying "Sherry" Lee, decided to investigate.
During the development of red blood cells, specialized bone marrow stem cells mature through several stages until they finally turn on the genes for hemoglobin and other red blood cell proteins and become mature red blood cells. In order to simulate this process in the lab, researchers have previously found that culturing blood cell progenitors in serum helps them turn on all of the proper proteins to take the final step and become a red blood cell.
Gao and Lee, now Principal Investigators at Westlake Institute for Advanced Study and Peking University, respectively, wondered if something in the serum was key to flipping the switch to becoming a mature red blood cell. To narrow down which of the molecules in the serum is the trigger, Gao and Lee ran the serum through a standard laboratory filter that many of us use everyday for our tap water: charcoal.
Long known for sucking odors out of the air and flavors from water, charcoal attracts and retains hydrophobic (water repellent) molecules. Gao and Lee noticed that once filtered, the serum no longer supported red blood cell production; they deduced that one of the hydrophobic molecules trapped by charcoal is the key to the final step of red blood cell maturation. Gao and Lee determined that when just the thyroid hormone thyroxin is added back to the serum, the red blood cell progenitors once again start down the path to maturation. Thyroid hormone's role is so important in stimulating red blood cell maturation, they discovered, that if it is added at an earlier stage of development, red blood cells short-circuit their usual developmental processes and begin turning into mature red blood cells.
Gao and Lee then teased apart the mechanism behind thyroid hormone's effect on red blood cell maturation. They pinpointed the specific type of receptor inside maturing red blood cells to which thyroid hormone binds. From there, they identified a protein that is necessary for thyroid hormone stimulation and that acts as a regulator of the final step of red blood cell production.
With this better understanding of the connection between thyroid hormone and red blood cell maturation, scientists may be able to identify new therapies that trigger red blood cells maturation in patients with specific types of anemia, including those with an underactive thyroid.
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 biological engineering at Massachusetts Institute of Technology (MIT). Lodish serves as a paid consultant and owns equity in Rubius, a biotech company that seeks to exploit the use of modified red blood cells for therapeutic applications.
"Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation"
PNAS; published ahead of print August 31, 2017
Xiaofei Gao (1,7), Hsiang-Ying Lee (1,7), Wenbo Li (2,3), Randall Jeffrey Platt (4,5), M. Inmaculada Barrasa (1), Russell R. Elmes (1), Michael G. Rosenfeld (2,3), and Harvey F. Lodish (1,4,6)
1. Whitehead Institute for Biomedical Research, Cambridge, MA 02142
2. Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093
3. Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093
4. Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139
5. Broad Institute of Harvard University and MIT, Cambridge, MA 02142
6. Department of Biology, MIT, Cambridge, MA 02139
7. Contributed equally to this work
Whitehead Institute for Biomedical Research
Related Red Blood Cells Articles:
Researchers have discovered that protection from the most severe form of malaria is linked with natural variation in human red blood cell genes.
Researchers have developed a new technique that uses modified insulin and red blood cells to create a glucose-responsive 'smart' insulin delivery system.
An international research team led by Osaka University built a novel 'Catch-Load-Launch' microfluidic device to monitor the resilience of red blood cells after being held in a narrow channel for various periods of time.
Researchers have generated the first immortalized cell lines which allow more efficient manufacture of red blood cells.
Using red blood cells modified to carry disease-specific antigens, a team of scientists from Whitehead Institute and Boston Children's Hospital have prevented and alleviated two autoimmune diseases -- multiple sclerosis (MS) and type 1 diabetes --i n early stage mouse models.
Scientists at the University of North Carolina at Chapel Hill have developed a breakthrough technique that uses light to activate a drug stored in circulating red blood cells so that it is released exactly when and where it is needed.
To better understand why some people adapt well to life at high altitude while others don't, researchers at University of California San Diego School of Medicine studied red blood cells derived from representatives of both groups living in the Andes Mountains.
A new treatment may diminish a dangerous side effect associated with transfusions of red blood cells (RBCs) known as pulmonary hypertension, an elevated blood pressure in the lungs and heart that can lead to heart failure, suggests a new study published in the November issue of Anesthesiology, the peer-reviewed medical journal of the American Society of Anesthesiologists (ASA).
For most stable hospitalized patients, transfusions of red blood cells stored for any time point within their licensed dating period -- so-called standard issue -- are as safe as transfusions with blood stored 10 days or less, or 'fresh,' according to updated clinical guidelines issued by an expert panel convened by a national organization that has long set standards for blood banking and transfusion practices.
In a report published online by JAMA, Jeffrey L. Carson, M.D., of Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., and colleagues provide recommendations for the AABB (previously known as the American Association of Blood Banks) for the target hemoglobin level for red blood cell (RBC) transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion.
Related Red Blood Cells Reading:
The Red Blood Cell: Volume I (1974-01-28)
by unknown (Author)
The Red Blood Cell: Volume I
by Douglas MacN. Surgenor (Editor)
The Red Blood Cell: Second Edition, Volume II (Volume 2)
by Douglas MacN. Surgenor (Editor)
Journal Pages - Red Blood Cell: 6" x 9", lined journal, blank book notebook, durable cover,150 pages for writing
by Journal Pages (Author), Blank Lined Journal (Author)
Your #1 Journal for writing your Life's Journey. This blank 150 page journal will jump start your creativity with its minimal design and bright white pages. It can be used for writing notes, as a diary, notebook to track your food, exercise or just for writing down important information.
This Blank Lined Journal is a perfect gift for all occasionsView Details
Pathophysiology of Blood Disorders (Lange Medical Books)
by Howard Franklin Bunn (Author), Jon C. Aster (Author)
A concise full-color review of the mechanisms of blood diseases and disorders – based on a Harvard Medical School hematology course
2015 Doody's Core Title!
4 STAR DOODY'S REVIEW!
"This is a superb book. Deceptively small, yet packs a wallop. The emphasis on principles instead of practice is welcome....The text is clear, concise, and surprisingly approachable for what could have been a very dense and dry discussion. I could not put this book down and read it entirely in one sitting. When was the last time anyone found a hematology textbook so... View Details
Red and White Blood Cells! What, How and Why of Human Cells - Body Chemistry Edition - Children's Clinical Chemistry Books
by Pfiffikus (Author)
Let’s get as tiny as the cells and go on a trip around the human body. Meet and greet the red and white blood cells. Did you know that although they interact with each other on a daily basis, these cells actually look different and they carry different functions? Knowledge of these functions will lead to a better understanding of how our body works. View Details
Red Blood Cell Aggregation
by Oguz Baskurt (Author), Björn Neu (Author), Herbert J. Meiselman (Author)
Red blood cells in humans―and most other mammals―have a tendency to form aggregates with a characteristic face-to-face morphology, similar to a stack of coins. Known as rouleaux, these aggregates are a normally occurring phenomenon and have a major impact on blood rheology. What is the underlying mechanism that produces this pattern? Does this really happen in blood circulation? And do these rouleaux formations have a useful function?
The first book to offer a comprehensive review of the subject, Red Blood Cell Aggregation tackles... View Details
My First Human Body Book
by Patricia J. Wynne (Author), Donald M. Silver (Author)
Here's the most entertaining way for children to learn how the human body works: 28 fun and instructive, ready-to-color illustrations that explore the muscular, skeletal, nervous, digestive, respiratory, and immune systems. Kids will discover how their voice box works, how many bones they have, how thousands of "tasters" on their tongues help them distinguish flavors, how the DNA in their cells is different from everyone else's, and so much more. Filled with astonishing details, this head-to-toe survey of the body is fascinating to read and fun to color! View Details
The Vitamin B12 Solution: Your Essential Key To Healthy Red Blood Cells And Anemia (Nutrition And Health) (Volume 2)
by Rossie C Pattison (Author)
Your Essential Key To Healthy Red Blood Cells And Anemia
Could a lack of vitamin B12 be the reason you're so tired or stressed? What if you were told that something found in your diet could prevent heart disease, memory loss or Alzheimer. If vitamin B12 deficiency is a concern, or you simply want to have a real understanding of this all too common issue, then The Vitamin B12 Solution is the one book that you should buy.
The Vitamin B12 Solution Your Essential Key to Healthy Red Blood Cells and Anemia is the authority on all such matters. It is written in a... View Details
When Red Blood Cells Leak
by Anne McMillen (Author)
Originally published in 2005 as a limited-edition chapbook, this volume contains 29 poems on violence, abuse, rage, and survival. View Details