Home » Stem Cell Technology » UCLA stem cell researchers discover “missing link”

stem cell
September 2, 2012
By: Robin Wulffson, M.D.

UCLA researchers have discovered a type of cell that is the “missing link” between bone marrow stem cells and all the cells of the human immune system. They note that their discovery will lead to a greater understanding of how a healthy immune system is produced and how disease can lead to poor immune function. They published their findings on September 2 in the early online edition of the journal Nature Immunology.

The researchers conducted their studies using human bone marrow, which contains all the stem cells that produce blood after birth. “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,” explained study senior author Dr. Gay Crooks, co-director of the Eli and Edythe Broad Center of Regenerative Medicine and a co-director of the Cancer and Stem Cell Biology program at UCLA’s Jonsson Comprehensive Cancer Center. She added, “The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of postnatal life.” She noted that the research team was “intrigued to find this particular bone marrow cell because it opens up a lot of new possibilities in terms of understanding how human immunity is produced from stem cells throughout life.”

The finding has implications for cancer treatment because understanding the process of normal blood formation in human adults is a crucial step in shedding light on what goes wrong during the process that results in leukemia (cancer of the blood). Before conducting this study, the researchers had a fairly good understanding of how to locate 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 intermediate stages of development called progenitors, which make various blood lineages such as red blood cells or platelets. The researchers were 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 the stem cells, the progenitor cells are also very rare, so before we can study them we needed to find the needle in the haystack.” explained first author Lisa Kohn, a member of the UCLA Medical Scientist Training Program. She noted that previous research had found a fairly mature type of lymphocyte progenitor with a limited ability to differentiate; however, the new study describes a more primitive type of progenitor primed to produce the entire immune system.

After identifying the lymphoid primed progenitor, the investigators studied how gene expression changed during the earliest stages of its production from stem cells. Dr. Crooks explained, “The gene expression data convinced us that we had found a unique stage of development in the immune system. 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.”

Dr. Crooks is a bone marrow transplant clinician who treats children with many diseases including leukemia and immune deficiency; therefore. She is keenly interested in how the immune system is made and, more specifically, any novel ways there may be to speed that process along in her patients, whose immune systems are wiped out prior to the transplant. The study authors wrote, “The identification of a progenitor in human bone marrow primed for full lymphoid differentiation will now permit delineation of the molecular regulation of the first stages of lymphoid commitment in human hematopoiesis,” the study states. “It will also allow understanding of how these processes are affected during aberrant hematopoiesis in disease states.”



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