title: Querkopf is a key marker of self-renewal and multipotency of adult neural stem cells.
abstract: Adult neural stem cells (NSCs) reside in the subventricular zone (SVZ) and produce neurons throughout life. Although their regenerative potential has kindled much interest, few factors regulating NSCs in vivo are known. Among these is the histone acetyltransferase querkopf (QKF, also known as MYST4, MORF, KAT6B), which is strongly expressed in a small subset of cells in the neurogenic subventricular zone. However, the relationship between Qkf gene expression and the hierarchical levels within the neurogenic lineage is currently unknown. We show here that the 10% of SVZ cells with the highest Qkf expression possess the defining NSC characteristics of multipotency and self-renewal and express markers previously shown to enrich for NSCs. A fraction of cells expressing Qkf at medium to high levels is enriched for multipotent progenitor cells with limited self-renewal, followed by a population containing migrating neuroblasts. Cells low in Qkf promoter activity are predominantly ependymal cells. In addition, we show that mice deficient for Bmi1, a central regulator of NSC self-renewal, show an age-dependent decrease in the strongest Qkf-expressing cell population in the SVZ. Our results show a strong relationship between Qkf promoter activity and stem cell characteristics, and a progressive decrease in Qkf gene activity as lineage commitment and differentiation proceed in vivo.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Victoria,  Australia.
authors.forename: Bilal N
authors.initials: BN
authors.lastname: Sheikh
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Dixon
authors.forename: Tim
authors.initials: T
authors.lastname: Thomas
authors.forename: Anne K
authors.initials: AK
authors.lastname: Voss
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis; D058953:Neural Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D063150:Polycomb Repressive Complex 1 / Q000235:genetics; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D015415:Biomarkers; C489421:Bmi1 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; C485184:enhanced green fluorescent protein; C528900:glial fibrillary astrocytic protein, mouse; D049452:Green Fluorescent Proteins; D051548:Histone Acetyltransferases; C496555:Kat6b protein, mouse; D063150:Polycomb Repressive Complex 1