Photo by Aaron Logan
A new screening method has revealed genes that regulate how hematopoietic stem and progenitor cells (HSPCs) grow and thrive in mice.
Researchers used this method to uncover 17 genes that are regulators of hematopoietic stem cell transplant (HSCT).
Thirteen of these genes had never before been linked to HSPC engraftment.
The researchers reported their findings in the Journal of Experimental Medicine.
“We recognized that one barrier to improving [HSCT] is a lack of understanding of how [HSPCs] successfully grow in the challenged environment of transplant, so we set out to identify the genes that control this process,” said Shannon McKinney-Freeman, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
Dr McKinney-Freeman and her colleagues transplanted more than 1300 mice with shRNA-transduced HSPCs and searched for genes that regulate HSPC repopulation.
The team identified 17 such genes—Arhgef5, Armcx1, Cadps2, Crispld1, Emcn, Foxa3, Fstl1, Glis2, Gprasp2, Gpr56, Myct1, Nbea, P2ry14, Smarca2, Sox4, Stat4, and Zfp251.
For most of these genes, knockdown yielded a loss of function. The exceptions were Armcx1 and Gprasp2, whose loss enhanced HSPC repopulation.
“Our functional screen in mice is a first step to enhancing [HSCT],” Dr McKinney-Freeman said. “If we are to improve transplant outcomes in patients, we next need to study these identified genes and the molecules they specify in much more detail.”
“The more we understand the full scope of the molecular mechanisms that regulate stable engraftment of [HSPCs], the better equipped we will be to develop and clinically test novel therapies to improve health outcomes.”
