β1-integrin restricts astrocytic differentiation of adult hippocampal neural stem cells

Sarah M. Brooker*, Allison M. Bond, Chian-Yu Peng, John Kessler

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Integrins are transmembrane receptors that mediate cell-extracellular matrix and cell-cell interactions. The β1-integrin subunit is highly expressed by embryonic neural stem cells (NSCs) and is critical for NSC maintenance in the developing nervous system, but its role in the adult hippocampal niche remains unexplored. We show that β1-integrin expression in the adult mouse dentate gyrus (DG) is localized to radial NSCs and early progenitors, but is lost in more mature progeny. Although NSCs in the hippocampal subgranular zone (SGZ) normally only infrequently differentiate into astrocytes, deletion of β1-integrin significantly enhanced astrocyte differentiation. Ablation of β1-integrin also led to reduced neurogenesis as well as depletion of the radial NSC population. Activation of integrin-linked kinase (ILK) in cultured adult NSCs from β1-integrin knockout mice reduced astrocyte differentiation, suggesting that at least some of the inhibitory effects of β1-integrin on astrocytic differentiation are mediated through ILK. In addition, β1-integrin conditional knockout also resulted in extensive cellular disorganization of the SGZ as well as non-neurogenic regions of the DG. The effects of β1-integrin ablation on DG structure and astrogliogenesis show sex-specific differences, with the effects following a substantially slower time-course in males. β1-integrin thus plays a dual role in maintaining the adult hippocampal NSC population by supporting the structural integrity of the NSC niche and by inhibiting astrocytic lineage commitment.

Original languageEnglish (US)
Pages (from-to)1235-1251
Number of pages17
JournalGlia
Volume64
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Neural Stem Cells
Integrins
Dentate Gyrus
Astrocytes
Stem Cell Niche
Adult Stem Cells
Neurogenesis
Embryonic Stem Cells
Knockout Mice
Cell Communication
Sex Characteristics
Nervous System
Population
Extracellular Matrix
Maintenance

Keywords

  • Astrocytes
  • Hippocampus
  • Integrins
  • Neural stem cells
  • Neurogenesis

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Brooker, Sarah M. ; Bond, Allison M. ; Peng, Chian-Yu ; Kessler, John. / β1-integrin restricts astrocytic differentiation of adult hippocampal neural stem cells. In: Glia. 2016 ; Vol. 64, No. 7. pp. 1235-1251.
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β1-integrin restricts astrocytic differentiation of adult hippocampal neural stem cells. / Brooker, Sarah M.; Bond, Allison M.; Peng, Chian-Yu; Kessler, John.

In: Glia, Vol. 64, No. 7, 01.07.2016, p. 1235-1251.

Research output: Contribution to journalArticle

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