Querkopf is a key marker of self-renewal and multipotency of adult neural stem cells
Details
Publication Year 2012-01-15, Volume 125, Issue #2, Page 295-309
Journal Title
JOURNAL OF CELL SCIENCE
Publication Type
Journal Article
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.
Publisher
COMPANY OF BIOLOGISTS LTD
Keywords
ACUTE MYELOID-LEUKEMIA; ACUTE MONOCYTIC LEUKEMIA; CENTRAL-NERVOUS-SYSTEM; HISTONE ACETYLTRANSFERASE; MAMMALIAN FOREBRAIN; PROGENITOR CELLS; MOUSE-BRAIN; ZINC-FINGER; CBP GENES; MOZ
WEHI Research Division(s)
Development And Cancer
Rights Notice
© The Company of Biologists Ltd 2013


Creation Date: 2012-01-15 12:00:00
Last Modified: 0001-01-01 12:00:00
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