to a megakaryocyte (red)
Credit: Meng Zhao
For the first time, researchers have shown that hematopoietic stem cells (HSCs) can be directly controlled by their own progeny, megakaryocytes.
Preclinical experiments revealed that megakaryocytes maintain HSC quiescence during homeostasis and promote HSC regeneration after chemotherapeutic stress.
The discovery suggests megakaryocytes might be used to treat patients with low blood cell counts and to expand HSCs for transplant.
The researchers described these findings in Nature Medicine.
The team examined the relationship between megakaryocytes and HSCs in mouse bone marrow. And they discovered that, as a terminally differentiated progeny, megakaryocytes regulate HSCs by performing two previously unknown functions.
“Megakaryocytes can directly regulate the amount of hematopoietic stem cells by telling the cells when they need to keep in the quiescent stage and when they need to start proliferating to meet increased demand,” said study author Meng Zhao, PhD, of the Stowers Institute for Medical Research in Kansas City, Missouri.
The researchers found that the protein transforming growth factor B1 (TGF-B1), contained in megakaryocytes, signaled quiescence.
And, when under stress from chemotherapy, megakaryocytes signaled fibroblast growth factor 1 (FGF1), to stimulate HSC proliferation.
“Our findings suggest that megakaryocytes are required for the recovery of hematopoietic stem cells post-chemotherapy,” said Linheng Li, PhD, also of the Stowers Institute.
The discovery could provide insight for using megakaryocyte-derived factors, such as TGF-B1 and FGF1, clinically to facilitate the regeneration of HSCs, he added.
Engineering a megakaryocyte niche that supports the growth of HSCs in culture is the next step for the researchers. They are also investigating whether a megakaryocyte niche can be used to help expand human HSCs in vitro for transplant.
These findings are supported by similar research also reported in Nature Medicine.
