Comprehensive map of human hematopoietic stem cell development created in world-first

Researchers from University of California, Los Angeles (UCLA; CA, USA) have developed a map that outlines the stages of blood stem cell development in the human embryo. The map will supply scientists with a blueprint for creating fully functioning hematopoietic stem cells in the lab.

The findings were recently published in the journal Nature and the research team suggested that the results may produce further clinical options for blood cancers or disorders. Hematopoietic stem cells are able to make unlimited copies of themselves and can differentiate into every type of blood cell in the body.

Hanna Mikkola, professor of molecular, cell and developmental biology at UCLA and lead investigator of the study, stated: “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.”

The research team developed the map using single-cell RNA sequencing and spatial transcriptomics, which are new techniques that allow scientists to pinpoint the unique genetic networks and functions of thousands of individual cells and to reveal the location of these cells in the embryo.

The novel techniques meant the researchers could plot hematopoietic stem cells as they emerged from the hemogenic endothelium. They were also able to track the migration of the cells during their development, starting at the aorta and arriving in the bone marrow. The map also reveals specific milestones in the maturation process of hematopoietic stem cells.

Researchers also reported that they have identified the specific precursor in the blood vessel wall that produces hematopoietic stem cells. This discovery resolves a historic debate around the stem cells’ cellular origin and the necessary conditions to create a blood stem cell rather than a hematopoietic progenitor cell.

Mikkola reflected: “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, 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.”

The research team claimed that the map can be utilized by scientists to understand how blood forming cells that are created in the embryo might contribute to human disease. This may lead to the discovery of further treatments for blood disorders or cancers in the future.

Source: Calvanese V, Capellera-Garcia S, Ma F, et al. Mapping human haematopoietic stem cells from haemogenic endothelium to birth. Nature. doi: 10.1038/s41586-022-04571-x (2022) (Epub ahead of print).

Press release: https://newsroom.ucla.edu/releases/map-human-blood-stem-cell-development