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

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. GLIA 2016;64:1235-1251.

Bifunctional Hydrogels Containing the Laminin Motif IKVAV Promote Neurogenesis

“…IKVAV/PL synergism was found to increment focal adhesions containing β 1 -integrin in embryonic cortical neurons, particularly on their neurites, providing a mechanistic explanation for the observed increase in overall cell adhesiveness and enhanced neurite outgrowth. This is in line with previous studies showing that β 1 -integrin promotes neurogenesis and enhances proliferation upon expression of a constitutively active β 1 -integrin in the embryonic chick mesencephalon ( Long et al., 2016 ), and that ablation of β1-integrin leads to reduced neurogenesis from hippocampal NSCs ( Brooker et al., 2016 ).…”

EMSCs Build an All‐in‐One Niche via Cell–Cell Lipid Raft Assembly for Promoted Neuronal but Suppressed Astroglial Differentiation of Neural Stem Cells

“…Laminin and fibronectin are known to promote neural differentiation. Integrin‐β1 showed a role in inducing neurogenesis by supporting the structural integrity of the NSC niche and inhibiting the astrocytic lineage commitment of NSCs . Moreover, we revealed that the Young's modulus of the living EMSC surface was 8.62 ± 2.37 kPa, a value that is significantly closer to the stiffness of the spinal cord tissue (50–200 Pa) than that of coverslips (average Young's modulus of 12.31 ± 3.99 MPa) (Figure d), suggesting that EMSCs possess desirable mechanical properties for nerve regeneration.…”

Intracellular signaling similarity reveals neural stem cell‐like properties of ependymal cells in the adult rat spinal cord

“…Beta1-integrins are reported to be upregulated in SCEp cells, and the differentiation of SCEp cells into astrocytes is promoted in the conditional knockout of beta1-integrins (North, Pan, Mcguire, Brooker, & Kessler, 2015). The conditional knockout of beta1-integrins in hippocampal NSCs also causes a similar differentiation tendency (Brooker, Bond, Peng, & Kessler, 2016), indicating the similarity of intracellular signaling between NSCs and SCEp cells. Campos, Decker, Taylor, & Skarnes (2006) presented that beta1-integrins mediate Notch signaling and cooperate with tyrosine kinase of the growth factor receptor to regulate the self-renewal of NSCs, demonstrating that Notch is the key regulator that mediates the extrinsic signal to intracellular transcriptional response in NSCs.…”

“…The conditional knockout of beta1-integrins in hippocampal NSCs also causes a similar differentiation tendency(Brooker, Bond, Peng, & Kessler, 2016), indicating the similarity of intracellular signaling between NSCs and SCEp cells Campos, Decker, Taylor, & Skarnes (2006). The conditional knockout of beta1-integrins in hippocampal NSCs also causes a similar differentiation tendency(Brooker, Bond, Peng, & Kessler, 2016), indicating the similarity of intracellular signaling between NSCs and SCEp cells Campos, Decker, Taylor, & Skarnes (2006).…”