Lrig1 expression prospectively identifies stem cells in the ventricular-subventricular zone that are neurogenic throughout adult life

Abstract

Background: Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) regulates stem cell quiescence. As a marker, it identifies stem cells in multiple organs of the mouse. We had detected Lrig1 expression in cultured Id1 high neural stem cells obtained from the lateral walls lining the lateral ventricles of the adult mouse brain. Thus, we investigated whether Lrig1 expression also identifies stem cells in that region in vivo. Methods: Publicly available single cell RNA sequencing datasets were analyzed with Seurat and Monocle. The Lrig1+ cells were lineage traced in vivo with a novel non-disruptive co-translational Lrig1 T2A-iCreERT2 reporter mouse line. Results: Analysis of single cell RNA sequencing datasets suggested Lrig1 was highly expressed in the most primitive stem cells of the neurogenic lineage in the lateral wall of the adult mouse brain. In support of their neurogenic stem cell identity, cell cycle entry was only observed in two morphologically distinguishable Lrig1+ cells that could also be induced into activation by Ara-C infusion. The Lrig1+ neurogenic stem cells were observed throughout the lateral wall. Neuroblasts and neurons were lineage traced from Lrig1+ neurogenic stem cells at 1 year after labeling. Conclusions: We identified Lrig1 as a marker of long-term neurogenic stem cells in the lateral wall of the mouse brain. Lrig1 expression revealed two morphotypes of the Lrig1+ cells that function as long-term neurogenic stem cells. The spatial distribution of the Lrig1+ neurogenic stem cells suggested all subtypes of the adult neurogenic stem cells were labeled.

LRIG1-Mediated Inhibition of EGF Receptor Signaling Regulates Neural Precursor Cell Proliferation in the Neocortex

“…A final question is whether LRIG1 is important for maintenance of quiescent adult NSCs where it is also expressed at lower levels, as described here and by Nam and Capecchi (2020). We show here that EGFR is the primary target for LRIG1 in developing NSCs, but EGFR is expressed only in activated and not quiescent adult NSCs.…”

CD36 and CD97 in Pancreatic Cancer versus Other Malignancies

“…Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) regulate cultured neural stem cell quiescence. The marker was identified in multiple organs in mice [224], but there is only a paper examining Lrig1 in pancreatic cancer [225].…”

A novel stem cell type at the basal side of the subventricular zone maintains adult neurogenesis

“…Finally, both groups of G + cells expressed similar transcripts level of the Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) gene (Fig. SD), which has been recently established as a marker for the prospective identification of NSCs in the V-SVZ (Nam & Capecchi, 2020). Primary cilia are closely linked to cell cycle progression and signal transduction (Goto et al, 2013).…”

“…Although the first attempts at NSC identification disagreed on the nature of NSCs, they both proposed apical cells as the main source of neurogenesis in the adult brain (Doetsch et al 1999; Johansson et al 1999). Despite the increasing range of approaches and markers used in earlier studies, the view that adult NSCs represent radial glia-like cells, has been maintained (Beckervordersandforth et al 2010; Codega et al 2014; Nam and Capecchi 2020). In contrast with this view, we here provide several lines of evidence of the additional existence of basal NSCs in the adult V-SVZ.…”