Protein That Organizes DNA Also Responsible for the Healthy Functioning of Blood Stem Cells, Study Shows

Researchers from Weill Cornell Medicine have identified a protein responsible for the way DNA is wrapped inside the chromosomes and how it plays a significant role in the healthy functioning of blood stem cells.

This protein, known as histone H3.3, enables DNA to be tightly compacted and serves as a platform for epigenetic or small chemical modifications that can either tighten or loosen the wrapped DNA to control local gene activity. Researchers of the new study examined how it affects blood stem cells.

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Assistant Professor of Genetics and Developmental Biology Stormy Chamberlain holds a tray of stem cells at the University of Connecticut`s (UConn) Stem Cell Institute at the UConn Health Center.

Blood Stem Cells Among the Most Studied Stem Cells

Blood stem cells are also known as hematopoietic stem cells (HSCs). A 2006 paper published in Methods Enzymol reported that HSCs have been a major focus of scientific efforts to make stem cell-based medical treatments, making them one of the most studied stem cells.

HSCs can give rise to other cell types, such as red blood cells, T cells, platelets, B cells, and pathogen-engulfing macrophages. They can self-renew and have the potential to identify all the mature blood cell types. Further understanding of how HSCs work could lead to many applications, such as better treatment for cancer.

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Understanding Self-Renewal Process of HSCs at the Molecular Level

In the study titled "Histone Variant h3.3 Maintains Adult Haematopoietic Stem Cell Homeostasis by Enforcing Chromatin Adaptability" published in Nature Cell Biology, researchers examined the role of the histone H3.3 in HSCs.

According to Science Daily, HSCs typically stay in a stem-like uncommitted state to survive long-term while slowly self-renewing. But some of them mature to produce other types of blood cells. Researchers found that the protein H3.3 plays a crucial role in both processes.

Study co-senior author Dr. Shahin Rafii said that how HSCs coordinate themselves to self-renew and differentiate into various blood cell types has been a mystery in biology. The findings of the new study help scientists understand blood stem cells at the molecular level and give new clues for future investigations.

The protein H3.3 has been a major focus of interest for biologists because of its crucial role in HSCs and other stem cells. Researchers said that the protein is composed of H3.3A and H3.3B genes that they used to genetically engineer their mice models to see what happens if H3.3 is not present.

They found that H3.3 absence in adulthood causes a depletion of self-renewing HSCs and affects the ability of the blood stem cells to differentiate into mature blood cell types with an atypical skewness or bias to white blood cells. More so, they observed that H3.3's deletion caused loss of epigenetic marks, adding to the evidence that the protein act as a master regulator of HSCs.

Why Is There an Increase Focus on Stem Cells?

Scientists have been studying stem cells for a variety of reasons. According to Mayo Clinic, studying stem cells help increase understanding of how diseases and conditions develop. By doing so, they would be able to study how to generate healthy cells to replace diseased cells.

People who have undergone stem cell therapies include patients with spinal cord injuries, type 1 diabetes, amyotrophic lateral sclerosis, Alzheimer's disease, heart disease, stroke, Parkinson's disease, cancer, and osteoarthritis.

Lastly, studying stem cells allows testing new drugs for safety and effectiveness. Researchers use some stem cells to test the quality of drugs to know how accurately they can cure diseases.