Zebrafish: Our Blood Relatives


By Amaris Garcia | UTS Writer | SQ Online (2013-14)

The trillions of blood cells that are rushing through your veins originated from a single type of stem cell in your bone marrow in a developmental process called hematopoiesis. The stem cell responsible for producing 2.5 billion red blood cells, 2.5 billion clotting platelets, and 50-100 billion white blood cells daily is called the hematopoietic stem cell (HSC).

HSCs are heavily studied because of their role in therapy for patients with immune system disorders, blood disorders, and cancer. Dr. David Traver’s lab at UCSD conducts research that is focused on studying hematopoietic stem cell emergence, maintenance, and differentiation in hopes that the data will improve human therapies to treat blood diseases.

Dr. David Stachura, a postdoctoral scholar working in the Traver lab, said “the whole goal of all our research is basically to be able to treat hematopoietic diseases like anemia or leukemia; things that involve blood production.”

To progress toward this goal, Dr. Stachura is researching hematopoiesis in zebrafish. Stachura previously studied mice hematopoiesis but then transition into researching zebrafish. Dr. Stachura said in one of his articles that zebrafish are “an increasingly popular model for understanding vertebrate hematopoiesis” because they “possess the same major blood lineages found in mammals, enabling comparative studies.”

There is an additional benefit that comes with using zebrafish as a model.

“The development of HSCs only occur during a certain embryonic period. The reason we use fish is because they develop outside of the parent’s body as opposed to mammals in a fetus,” said Stachura. “Zebrafish eggs are transparent and therefore allow us to watch the hematopoietic stem cells under a microscope.”

Stachura began his research by examining growth factors, called cytokines, that are related to the formation of blood cells.

“What I’ve been doing is studying…cytokines and their role in producing blood cells and how they regulate the production of blood cells. That’s how we started studying hematopoiesis,” said Stachura.

Specifically, Stachura is researching granulocyte colony stimulating factors (Gcsfs) and their function in zebrafish.

These are in vitro blood cell colonies grown in the presence of Gcsf.  The green colony  is myeloid (bone marrow cells), the red colony is erythroid (red blood cells), and the red/green colony has both myeloid and erythroid cells. Photo courtesy of Dr. David Stachura.

These are in vitro blood cell colonies grown in the presence of Gcsf. The green colony is myeloid (bone marrow cells), the red colony is erythroid (red blood cells), and the red/green colony has both myeloid and erythroid cells.
Photo courtesy of Dr. David Stachura.

Previously, zebrafish were thought to possess only one copy of the Gcsf ligand, but Stachura found another ligand exists that is parallel in placement and sequence to the human chromosome. However, the ligand’s function in zebrafish is not exactly the same as it is in humans.

“Gcsf signaling [in zebrafish] is required for HSC specification and expansion, roles that have not been described for mammalian Gcsf,” Stachura said, in a recent article.

The ligand in zebrafish has a broader function than in humans, suggesting that during the evolution of mammals, other cytokines took on more specific roles in humans. Nevertheless, the research recognizes that Gcsf is important in human hematopoiesis and the fact remains that the gene sequence for zebrafish mirror that of advanced mammal genes. This research shows that humans are related to zebrafish in terms of blood formation.

The convenience of zebrafish as models and the newly discovered genetic similarities are important contributors to the ultimate goal of finding cures for blood diseases. Data from these studies could elucidate mechanisms to help human HSCs during treatment of diseases.

The ability to manipulate and monitor hematopoietic stem cells in zebrafish is advantageous to drug studies. The hope is to discover how to most effectively treat or even cure blood diseases by correcting or replacing impaired HSCs, which would repair adult hematopoiesis.

In the United States alone, more than three million people are afflicted with anemia and an estimated 287,963 people have leukemia. With increasing knowledge about hematopoietic stem cells, it is hopeful that the number of people suffering from blood diseases will diminish.