Clonogenic mast cell progenitors and their excess numbers in chimeric BALB/c mice with inactivated GATA-1.
In agar cultures of marrow cells from adult female BALB/c chimeric GATA-1(Plt13/+) mice, a high frequency of unusual dispersed colonies was noted. Analysis showed that these were colonies of mast cells and that mast cell colony-forming cells (progenitors) could be detected in clonal cultures of adult marrow, neonatal marrow, or fetal liver if the combined stimulus of stem cell factor and interleukin-3 was used. Mast cell progenitors were in active cell cycle and showed an extensive capacity for self-generation. Mast cell colonies both from control GATA-1(+/+) mice and GATA-1(Plt13/+) mice could generate growth factor-dependent cloned cell lines that grew for >18 months. Surprisingly, the majority of the excessive numbers of mast cell progenitors in chimeric GATA-1(Plt13/+) mice were transcribing the inactive Plt13 allele of GATA-1, suggesting that GATA-1 normally acts to restrict the emergence of committed mast cell progenitors. In sharp contrast, all eosinophil progenitors in these mice were transcribing the normal GATA-1 allele. No excess tissue mast cells were observed in GATA-1(Plt13/+) mice, suggesting that the excess mast cell progenitors in these mice might be generating mast cells with a defective in vivo proliferative or tissue homing capacity.
Metcalf
Donald
D
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Victoria, Australia. metcalf@wehi.edu.au
Majewski
Ian
I
Mifsud
Sandra
S
Di Rago
Ladina
L
Alexander
Warren S
WS
D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D004804:Eosinophils / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D005838:Genotype; D006412:Hematopoietic Stem Cells; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
D050982:GATA1 Transcription Factor