CHOP researchers find ribosome assembly essential for stem cell regeneration
Findings enhance our understanding of the importance of ribosome assembly in stem cell regeneration and potential therapeutic strategies for ribosomopathies, which lead to pediatric bone marrow abnormalities
2021-03-11
(Press-News.org) Philadelphia, March 11, 2021--Researchers at Children's Hospital of Philadelphia (CHOP) have identified genes responsible for hematopoietic stem cell (HSC) regeneration via the assembly of the ribosome, the protein factories in cells that translate mRNA sequences into amino acid sequences. The findings, which were published in Cell Stem Cell, highlight the importance of proper ribosome assembly in stem cell regeneration and identify possible targets for future therapies for ribosomopathies, childhood disorders that lead to bone marrow failure (BMF).
"Although previous research showed that mutations that affect ribosome assembly are associated with human diseases that involve bone marrow dysfunction, how ribosome assembly is regulated in hematopoietic stem cells and how it contributes to disease was poorly understood," said Wei Tong, PhD, investigator and Professor of Pediatric Hematology at CHOP and senior author of the paper. "This study has identified the mechanism that prevents ribosomes from assembling properly in mammals, leading to insufficient hematopoietic stem cells, which could potentially be exploited in future therapeutic interventions."
Ribosomopathies describe a group of inherited BMF syndromes with impaired ribosome function. Individuals with ribosomopathies are deficient in HSCs but are also predisposed to elevated leukemia and cancer risks. Shwachman-Diamond syndrome (SDS), a rare pediatric blood disorder that affects the pancreas, bone marrow, and skeleton, is an example of a BMF syndrome that is linked to ribosome dysfunction arising from mutations of ribosome assembly factors. Understanding how ribosomal abnormalities lead to BMF and cancer predisposition is essential in developing treatments for these disorders, yet prior to this study, researchers had little evidence of how assembly factors themselves are regulated and how they impact hematopoietic regeneration in mammals.
Working in a mouse model, the researchers identified the E3 ubiquitin ligase HectD1 as playing a key role in regulating HSC function via ribosome assembly and protein translation. Ribosome assembly involves bringing a large subunit together with a small subunit in order to translate mRNA into proteins. Assembly factors help this process occur, including one called ZNF622 in the large subunit. In HSCs under stress conditions, such as inflammation or injury, HectD1 tags ZNF622 for destruction, allowing ribosome assembly to occur. However, cells that lack the Hectd1 gene accumulate ZNF622 because it is no longer tagged for destruction, which prevents the large and small subunits from joining.
The researchers also found that knocking out the Znf622 gene in Hectd1-deficient HSCs restored the ability of the large and small subunits to join properly, leading to restored protein synthesis and HSC production.
"These findings not only highlight the connection between protein degradation, ribosome assembly, and stem cell production, but they also reveal the potential for knocking down Znf622 to restore proper bone marrow function, which is critical for child development," Tong said. "Future research should look at this mechanism as a potential target for patients with these disorders."
INFORMATION:
Funding for this work was provided the National Institutes of Health, the Department of Defense, St. Baldrick's Foundation, Alex's Lemonade Research Foundation, and the Basser Center for BRCA Research, among others.
Kaosheng Lv et al. "HectD1 Controls Hematopoietic Stem Cell Regeneration by Coordinating Ribosome Assembly and Protein Synthesis," Cell Stem Cell, online March 11, 2021, DOI: 10.1016/j.stem.2021.02.008
About Children's Hospital of Philadelphia: Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. In addition, its unique family-centered care and public service programs have brought the 595-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
2021-03-11
BOSTON - In the last two decades, immunotherapy has emerged as a leading treatment for advanced renal carcinoma cancer (more commonly known as kidney cancer). This therapy is now part of the standard of care, but it doesn't work for all patients, and almost all patients, no matter how they respond initially, become more resistant to treatment over time. The immune system plays a critical role in kidney cancer disease progression and in response to therapies, and so a fundamental challenge in the field is to understand the underlying "immune circuitry" of this disease.
In two new studies published today in Cancer Cell, researchers from Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard used the emerging ...
2021-03-11
For decades, researchers assumed the cosmic rays that regularly bombard Earth from the far reaches of the galaxy are born when stars go supernova -- when they grow too massive to support the fusion occurring at their cores and explode.
Those gigantic explosions do indeed propel atomic particles at the speed of light great distances. However, new research suggests even supernovae -- capable of devouring entire solar systems -- are not strong enough to imbue particles with the sustained energies needed to reach petaelectronvolts (PeVs), the amount of kinetic energy attained by very high-energy cosmic rays.
And yet cosmic rays have been observed striking Earth's atmosphere at exactly those velocities, their passage marked, for example, by the detection ...
2021-03-11
CHAPEL HILL, NC - A first-of-its-kind study out today in JAMA Surgery suggests that patients have a more difficult time understanding and building trust with their surgeons when they cannot see the surgeon's entire face due to masking requirements. These findings have major implications for not only how surgeons are viewed and rated by their patients, but also how well a patient does during and after a surgical procedure.
"At beginning of pandemic I had a patient say, 'Dr. Kapadia, it's odd you've taken out a big part of my colon and I don't even know what you look like,'" Muneera Kapadia, MD, the study's senior author said. "It made me realize we don't have much information ...
2021-03-11
Volcanologists do what they can to provide the public enough warning about impending eruptions, but volcanoes are notoriously unpredictable. Alerts are sometimes given with little time for people to react.
That may soon change.
Work led by research assistant professor Társilo Girona, with the University of Alaska Fairbanks Geophysical Institute, has revealed a method by which scientists -- and the public -- can have perhaps years of advance warning about a potential eruption.
The solution lies in regular and widespread monitoring of the radiant temperature of a volcano's flanks before the appearance of any of the usual warning ...
2021-03-11
DALLAS, March 11, 2021-- Silent heart attacks appear to increase stroke risk in adults 65 and older, according to preliminary research to be presented at the American Stroke Association International Stroke Conference 2021. The virtual meeting is March 17-19, 2021 and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.
A silent heart attack, also known as a silent myocardial infarction, has no, minimal or unrecognized symptoms. An electrocardiogram (ECG) or some form of imaging of the heart like ...
2021-03-11
DALLAS, March 11, 2021 -- Black and Hispanic women ages 65-74 years old hospitalized with stroke had more severe strokes than their white counterparts, according to preliminary research to be presented at the American Stroke Association International Stroke Conference 2021. The virtual meeting is March 17-19, 2021 and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.
According to the American Heart Association, Black women have a higher rate of stroke (3.8%) when compared to white women (2.5%) of similar age, which could lead to a higher death rate or worse quality of life.
"The Black and Hispanic female stroke survivors 65-84 years old were younger and had ...
2021-03-11
Polarization control is essential for tailoring light-matter interactions and is the foundation for many applications such as polarization imaging, nonlinear optics, data storage, and information multiplexing. A linear polarizer, which is a polarization optical element that filters a specific linear polarization from unpolarized light, plays an important role in both polarization generation and manipulation. However, the generation of arbitrary polarization states other than linear polarization usually requires cascading of multiple optical polarization elements, ...
2021-03-11
In contemporary society, the demand for high-bandwidth optical communication, including mobile high-definition videos, autonomous vehicles, remote surgery, telepresence, and interactive 3D virtual reality gaming, is sharply increasing. The electro-optical modulator is the key component for optical fiber communication, which modulates the light signal for loading information through electricity. Lithium niobate (LiNbO3, LN) exhibits a high-performance electro-optic effect and high optical transparency. On the other hand, the ferroelectric domain engineering on LN crystals has been ...
2021-03-11
A team of researchers from the Agency for Science, Technology and Research's (A*STAR) Genome Institute of Singapore (GIS) have developed a CRISPR-based gene editor, C-to-G Base Editor (CGBE), to correct mutations that cause genetic disorders. Their research was published in Nature Communications on 2 March 2021.
One in seventeen people in the world suffers from some type of genetic disorder. Chances are, you or someone you know - a relative, friend, or colleague - is one of approximately 450 million people affected worldwide. Mutations responsible for these disorders can be caused by ...
2021-03-11
The Healthy Diet Index developed by Finnish nutrition experts facilitates the assessment of diet quality. Its effectiveness was demonstrated in a recently published study.
Dietary counselling plays a crucial role in the prevention and treatment of chronic lifestyle diseases. In healthcare settings, dietary counselling is often provided by professionals without specific training in nutrition, and there is a demand for tools for reliable and easy assessment of diet quality. One such tool is the Healthy Diet Index developed in the recently completed Stop Diabetes (StopDia) project.
The Healthy Diet ...
LAST 30 PRESS RELEASES:
[Press-News.org] CHOP researchers find ribosome assembly essential for stem cell regeneration
Findings enhance our understanding of the importance of ribosome assembly in stem cell regeneration and potential therapeutic strategies for ribosomopathies, which lead to pediatric bone marrow abnormalities
