Map of Human Blood Stem Cell Development Created

Stem cells dividing, illustration
Stem cells. Illustration of bone marrow stem cells dividing. Bone marrow stem cells are multipotent cells that can differentiate into a variety of cell types, including white blood cells, red blood cells, cartilage cells and bone cells.

Researchers based at the University of California, Los Angeles (UCLA) have created a detailed map of human blood cells and how they develop in an embryo, which could help improve treatments for blood-related disorders like leukemia and sickle-cell disease in the future.

Hematopoietic stem cells are the early version of blood cells in the body and are able to make unlimited copies of themselves and change into every type of blood cell in the body. In adults, this process occurs in the bone marrow, which is the reason bone marrow transplants have been used for years as a way to treat people with serious blood disorders. These cells can also be extracted from infant cord blood after birth.

However, while these transplants have saved many lives, there are never enough matched bone marrow donors available to treat all the patients needing this treatment and the number of stem cells in cord blood is low.

Researchers have attempted to create hematopoietic stem cells in the lab from human pluripotent stem cells, which theoretically can form any cell type in the body, but success has been limited to date.

“Nobody has succeeded in making functional blood stem cells from human pluripotent stem cells because we didn’t know enough about the cell we were trying to generate,” said lead researcher on this study Hanna Mikkola, a professor based at the UCLA Jonsson Comprehensive Cancer Center, in a press statement.

To combat this, Mikkola and colleagues created a map of hematopoietic stem cells and how they develop using single-cell RNA sequencing and spatial transcriptomics, a new method where cell types can be assigned locations depending on their RNA.

As described in the Nature paper about the work, the team was able to track the hematopoietic stem cells from when they first emerged from the hemogenic endothelium and as they move from one location to the other during their development, starting from the aorta and arriving in the bone marrow.

Something revealed by the map was that these cells go through the liver during development where they acquire the self-renewing abilities of hematopoietic stem cells, which differentiates them from short-lived blood progenitor cells that are limited in the number of cells they can differentiate into.

The researchers also discovered the exact precursor cell in the blood vessel wall that gives rise to hematopoietic stem cells, something that has long been debated by experts in the field.

“We now have a manual of how hematopoietic stem cells are made in the embryo and how they acquire the unique properties that make them useful for patients,” said UCLA scientist Vincenzo Calvanese, a co–first author of the research, who is also a group leader at University College London.

Information about the map and de-identified data can be found on The Atlas of Human Hematopoietic Stem Cell Development website. The researchers are now planning to use their data to try and create more viable transplantable hematopoietic stem cells in the lab, something that has been difficult until now.

“Previously, if we tried to create a blood stem cell from a pluripotent cell and it didn’t transplant, we wouldn’t know where in the process we failed,” Mikkola said. “Now, we can place the cells in our roadmap to see where we’re succeeding, where we’re falling short and fine-tune the differentiation process according to the instructions from the embryo.”

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