Abstract
Stem cell properties change over time to match the changing growth and regeneration demands of tissues. We showed previously that adult forebrain stem cell function declines during aging because of increased expression of let-7 microRNAs, evolutionarily conserved heterochronic genes that reduce HMGA2 expression. Here we asked whether let-7 targets also regulate changes between fetal and adult stem cells. We found a second let-7 target, the RNA binding protein IMP1, that is expressed by fetal, but not adult, neural stem cells. IMP1 expression was promoted by Wnt signaling and Lin28a expression and opposed by let-7 microRNAs. Imp1-deficient neural stem cells were prematurely depleted in the dorsal telencephalon due to accelerated differentiation, impairing pallial expansion. IMP1 post-transcriptionally inhibited the expression of differentiation-associated genes while promoting the expression of self-renewal genes, including Hmga2. A network of heterochronic gene products including Lin28a, let-7, IMP1, and HMGA2 thus regulates temporal changes in stem cell properties. DOI: http://dx.doi.org/10.7554/eLife.00924.001.
Highlights
Stem cell properties change throughout life in many tissues in response to changing growth and regeneration demands (He et al, 2009)
We examined Imp1 expression by quantitative RT-PCR in central nervous system (CNS) stem/progenitor cells from the embryonic day (E)12.5 dorsal telencephalon, E14.5 dorsal telencephalon, postnatal day (P)0 lateral ventricle ventricular zone (VZ), and P30 lateral ventricle subventricular zone (SVZ)
Imp1 expression was high at E12.5 but declined over 100-fold by P0 and was no longer detected in the P30 SVZ (Figure 1A)
Summary
Stem cell properties change throughout life in many tissues in response to changing growth and regeneration demands (He et al, 2009). These changes are evident in the central nervous system (CNS) forebrain, where neural stem cells persist throughout life. Quiescent neural stem cells persist into adulthood in the lateral wall of the lateral ventricle subventricular zone (SVZ) as well as in the dentate gyrus, where they give rise to new interneurons throughout adult life (Alvarez-Buylla and Lim, 2004; Zhao et al, 2008). A fundamental question concerns the mechanisms that control these temporal changes in stem cell properties
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