Capitano, Maegan L.Sammour, YasserRopa, JamesLegendre, MaureenMor-Vaknin, NiritMarkovitz, David M.2022-12-272022-12-272022Capitano, M. L., Sammour, Y., Ropa, J., Legendre, M., Mor-Vaknin, N., & Markovitz, D. M. (2022). DEK, a nuclear protein, is chemotactic for hematopoietic stem/progenitor cells acting through CXCR2 and Gαi signaling. Journal of Leukocyte Biology, 112(3), 449–456. https://doi.org/10.1002/JLB.3AB1120-740R0741-5400, 1938-3673https://hdl.handle.net/1805/30807Few cytokines/growth modulating proteins are known to be chemoattractants for hematopoietic stem (HSC) and progenitor cells (HPC); stromal cell-derived factor 1α (SDF1α/CXCL12) being the most potent known such protein. DEK, a nuclear DNA-binding chromatin protein with hematopoietic cytokine-like activity, is a chemotactic factor attracting mature immune cells. Transwell migration assays were performed to test whether DEK serves as a chemotactic agent for HSC/HPC. DEK induced dose- and time-dependent directed migration of lineage negative (Lin–) Sca-1+ c-Kit+ (LSK) bone marrow (BM) cells, HSCs and HPCs. Checkerboard assays demonstrated that DEK's activity was chemotactic (directed), not chemokinetic (random migration), in nature. DEK and SDF1α compete for HSC/HPC chemotaxis. Blocking CXCR2 with neutralizing antibodies or inhibiting Gαi protein signaling with Pertussis toxin pretreatment inhibited migration of LSK cells toward DEK. Thus, DEK is a novel and rare chemotactic agent for HSC/HPC acting in a direct or indirect CXCR2 and Gαi protein-coupled signaling-dependent manner.en-USAttribution-NonCommercial 4.0 InternationalchemokinesCXCR2Gαi signalinghematopoietic stem and progenitor cellsArticle