A network of heterochronic genes including Imp1 regulates temporal changes in stem cell properties

Jinsuke Nishino, Sunjung Kim, Yuan Zhu, Hao Zhu, Sean J. Morrison

Research output: Contribution to journalArticle

55 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere00924
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Nov 5 2013

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Adult Stem Cells
Gene Regulatory Networks
Stem cells
Stem Cells
Neural Stem Cells
Genes
MicroRNAs
Fetal Stem Cells
Telencephalon
RNA-Binding Proteins
Prosencephalon
Regeneration
Growth
Aging of materials
Tissue

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

A network of heterochronic genes including Imp1 regulates temporal changes in stem cell properties. / Nishino, Jinsuke; Kim, Sunjung; Zhu, Yuan; Zhu, Hao; Morrison, Sean J.

In: eLife, Vol. 2013, No. 2, e00924, 05.11.2013.

Research output: Contribution to journalArticle

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