Merocyanine 540 alters the self-renewal capacity of murine pluripotent hemopoietic stem cells.
Merocyanine 540 (MC 540), an impermeant photoreactive dye with a high affinity for the plasma membrane of hemopoietic precursors, was examined for effects on the self-replicative capacity (SR) of CFUS from normal mouse marrow, and on various CFUS subpopulations fractionated by velocity sedimentation. Brief exposure (30 s) of whole marrow to MC 540 resulted in a reduction in overall CFUS self-renewal in primary recipient spleens. Reduced self-renewal was also observed when fractionated CFUS subpopulations were used. Reduced self-renewal was not accompanied by obvious changes in primary spleen colony number or composition. MC 540 may interact with specific superficial membrane sites relevant to the SR process. Upon longer exposure, further MC 540 effects appear restricted to a reactive subpopulation of large (low SR) CFUS. Self-renewal was enhanced in this fractionated pool, without evidence of primary colony reduction, by intermediate staining. This strongly suggests that under certain conditions the dye can alter a fundamental functional property of susceptible stem cells, without their inactivation. Still more prolonged staining apparently leads to the selective elimination of this reactive low SR CFUS subset. A marked reduction in whole marrow-derived spleen colonies was accompanied by an enhanced self-renewal capacity among the survivors. These two MC 540 effects--stem cell modification, and stem cell elimination--may reflect different stages in an ongoing membrane photo-oxidation process.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011744:Pyrimidinones / Q000494:pharmacology*
D011744:Pyrimidinones; C003954:merocyanine dye