Researchers Uncover Missing Link Between Blood Stem Cells And Cells Of The Human Immune System

The research was done using human bone marrow, which contains all the stem cells that produce blood during post-natal life.

"We felt it was especially important to do these studies using human bone marrow, as most research into the development of the immune system has used mouse bone marrow," said Dr. Gay Crooks, co-director of UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. "The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of post-natal life."

Prior to this study researchers had a fairly good idea of how to find and study the blood stem cells of the bone marrow. The stem cells live forever, reproduce themselves and give rise to all the cells of the blood. In the process, the stem cells divide and produce cells in intermediate stages of development called progenitors, which make various blood lineages, like red blood cells or platelets. 

Crooks, who is also co-director of the cancer and stem-cell biology program at UCLA's Jonsson Comprehensive Cancer Center, was most interested in the creation of the progenitors that form the entire immune system, which consists of many different cells called lymphocytes, each with a specialized function to fight infection.

"Like stem cells, the progenitor cells are also very rare, so before we can study them, we needed to find the needle in the haystack," said Lisa Kohn, a member of the UCLA Medical Scientist Training Program.

 

Previous work had found a fairly mature type of lymphocyte progenitor with a limited ability to differentiate, but the new work describes a more primitive type of progenitor primed to produce the entire immune system, Kohn said.

Once the lymphoid-primed progenitor had been identified, Crooks and her team studied how gene expression changed during the earliest stages of its production from stem cells.
 
"The gene expression data convinced us that we had found a unique stage of development in the immune system," Crooks said. "There was a set of genes that the lymphoid-primed cell shares with the bone marrow stem cells and a unique gene expression of its own once it becomes active. This data provided us with an understanding of what genes are important in creating all the cells of the immune system. The information could allow us to manipulate bone marrow to help create a stronger immune system."
 
As a bone-marrow transplant clinician who treats children with many diseases, including leukemia and immune deficiency, Crooks is keenly interested in how the immune system is made and, more specifically, in potential new ways to speed that process along in her patients, whose immune systems are wiped out prior to transplant.

Adapted from the UCLA announcement.