Image by Ian Johnston
Zebrafish embryos
Experiments in zebrafish embryos have suggested that trunk neural crest cells play a key role in the specification of hematopoietic stem cells (HSCs).
Researchers believe this finding could be used to aid the creation of HSCs in the lab and ultimately help improve access to HSC transplant.
“The research will likely open new avenues of investigation in stem cell biology and blood development and provide insight to aid efforts to make transplantable hematopoietic stem cells in the lab,” said Wilson Clements, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
Dr Clements and Erich W. Damm, PhD, also of St. Jude, described this research in Nature Cell Biology.
The researchers noted that scientists have yet to achieve in vitro specification of normal HSCs with a high level of engraftment and normal multilineage potential. And this suggests key specification signals remain unknown.
The pair pointed out that, in all vertebrates, HSCs arise from hemogenic endothelium in the ventral floor of the dorsal aorta. And stromal cells residing in stem cell microenvironments often act as a niche to contribute cues that regulate behavior.
“Researchers have speculated that the endothelial cells that give rise to blood-forming stem cells are surrounded by a support niche of other cells whose identity and origins were unknown,” Dr Damm said. “Our results support the existence of a niche and identify trunk neural crest cells as an occupant.”
Trunk neural crest cells are made in the developing spinal cord and migrate throughout the embryo. The cells eventually give rise to a variety of adult cells, including neurons and glial cells in the sympathetic and parasympathetic nervous system.
Using time-lapse video, Drs Clements and Damm tracked the migration of neural crest cells in the transparent embryos of zebrafish. (Zebrafish and humans share nearly identical blood systems.)
After about 20 hours, the neural crest cells had reached the developing aorta. After hour 24, the migrating cells had cozied up to the endothelial cells in the aorta, which then turned on genes, such as runx1, indicating their conversion to HSCs.
Additional experiments revealed that migration of neural crest cells to the dorsal aorta is dependent on platelet-derived growth factor signaling, and this signaling is required for HSC specification.
Likewise, the physical association of neural crest cells with the pre-hematopoietic dorsal aorta is required for initiation of the hematopoietic program and HSC specification.
Drs Clements and Damm said these results suggest neural crest cells are key cellular components of the HSC specification niche that can be profiled to identify unknown HSC specification signals.
