The intron 5/6 promoter region of the ship1 gene regulates expression in stem/progenitor cells of the mouse embryo.
The s-SHIP protein is a shorter isoform of the longer SHIP1 protein and lacks the N-terminal SH2 domain region contained in SHIP1. s-SHIP is expressed in ES cells and in enriched bone marrow stem cells, and may be controlled by a promoter within intron 5 of the ship1 gene. We therefore examined the potential specificity of promoter activity in ES cells of an intron 5/intron 6 ship1 genomic segment and its tissue specificity within transgenic mice expressing GFP from this promoter region. The results indicate that s-SHIP promoter activity is specific for ES cells in vitro and for known and presumptive stem/progenitor cells throughout embryo development of the transgenic mice. Specific GFP expression was observed in the blastocyst, primordial germ cells, thymus, arterioles, osteoblasts, and skin epidermis. The epidermis/epithelium is the progenitor for hair follicles, mammary tissue, and prostate. Interestingly, each of these latter tissues acquired a few GFP-positive cells in the course of their development from the epithelial layers, and these cells express marker proteins for stem/progenitor cells. These results identify potential stem cell populations, mark these cells for analyses in normal and cancer development, and implicate s-SHIP as an important protein in stem/progenitor cell function.
Rohrschneider
Larry R
LR
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. lrohrsch@fhcrc.org
Custodio
Joseph M
JM
Anderson
Tamara A
TA
Miller
Chris P
CP
Gu
Hong
H
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D002460:Cell Line; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D000072181:Inositol Polyphosphate 5-Phosphatases; D007438:Introns; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009928:Organ Specificity; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000378:metabolism*; D019076:Transgenes
D049452:Green Fluorescent Proteins; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases