Induction of the murine “W phenotype” in long‐term cultures of human cord blood cells by c‐kit antisense oligomers

The murine white (W) spotting locus is the site of the c‐kit gene and encodes a tyrosine kinase receptor while the complementary Steel (Sl) iocus encodes its ligand. Mutations at either locus have profound effects on hematopoiesis, particularly erythroid and mast cell proliferation. We added c‐kit antisense oligonucleotides to long‐term suspension cultures of enriched human umbilical cord progenitor cells. This resulted in the suppression of c‐kit gene expression and the preferential suppression of the generation of erythroid burst‐forming cells (BFU‐E) which extended over the life of the culture (3 weeks). The results provide an in vitro model of the “W phenotype” in human hematopoiesis and confirm the importance of c‐kit gene function in early erythropoiesis. Because the generation of BFU‐E was suppressed even after c‐kit gene expression had recovered, this gene product may be critical to the erythroid commitment process. © 1993 Wiley‐Liss, Inc.

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