Researchers at the University of California, Los Angeles (UCLA) have unveiled a novel road map tracking blood stem cell development in the human embryo, findings that could help develop new treatments for blood cancers and inherited blood disorders.
The maturation map of blood stem cells—or hematopoietic stem cells—supplies a blueprint for creating fully functional blood stem cells in the lab. The online resource can be used by scientists worldwide.
Published April 13 in Nature, the research could help expand treatment options for blood cancers and disorders such as leukemia and sickle cell disease, according to Hanna Mikkola, M.D., Ph.D., study lead, professor in the UCLA College and member of the UCLA Jonsson Comprehensive Cancer Center.
For years, blood stem cells from donor bone marrow and umbilical cords have been used as life-saving transplant treatments for patients with blood and immune diseases. However, donor shortages and the low number of stem cells in cord blood mean only a limited number of treatments can be delivered.
Blood stem cells are able to reproduce unlimited copies and differentiate into every type of human blood cell. Researchers have attempted to create blood stem cells in the lab from human pluripotent stem cells without success.
“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,” Mikkola said in a news release.
The research team, which included scientists from Germany’s University of Tübingen and Australia’s Murdoch Children’s Research Institute, used single-cell RNA sequencing and spatial transcriptomics to create the map. The technology allowed for the identification of unique genetic networks and functions of individual cells and detection of location within the embryo.
“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-author of the research and group leader at University College London.
The data make it possible to follow blood stem cells as they start their travel from the hemogenic endothelium to the final destination in the bone marrow. The map shows specific milestones in the maturation process, including arrival in the liver, where cells acquire the special capabilities of blood stem cells.
“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.”
Other discoveries include pinpointing the precursor in the blood vessel wall that produces blood stem cells, a finding that clarifies uncertainty surrounding cellular origin. The map can also help scientists understand the role blood-forming cells developed in the embryo play for certain diseases.
Research was supported by the National Institutes of Health, the UCLA Jonsson Cancer Center Foundation, the David Geffen School of Medicine at UCLA, the Swedish Research Council, the European Molecular Biology Organization, the Swiss National Science Foundation and the UCLA Broad Stem Cell Research Center, as well as support from the Rose Hills Foundation.