Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112-5331, USA.
Neural Dev. 2020 Mar 17;15(1):3. doi: 10.1186/s13064-020-00139-5.
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 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.
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 reporter mouse line.
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.
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.
富含亮氨酸重复序列和免疫球蛋白样结构域 1（Lrig1）调节干细胞静止。作为一种标志物，它可以识别小鼠多个器官中的干细胞。我们曾在体外培养的 Id1 神经干细胞中检测到 Lrig1 的表达，这些干细胞来自成年小鼠脑侧脑室壁的侧部。因此，我们研究了 Lrig1 表达是否也能在体内识别该区域的干细胞。
使用 Seurat 和 Monocle 分析公共单细胞 RNA 测序数据集。通过一种新型非破坏性共翻译 Lrig1 报告小鼠系对 Lrig1+细胞进行体内谱系追踪。
单细胞 RNA 测序数据集的分析表明，Lrig1 在成年小鼠脑侧脑室壁的神经发生谱系中最原始的干细胞中高度表达。支持其神经干细胞身份的是，只有在两种形态上可区分的 Lrig1+细胞中观察到细胞周期进入，这两种细胞也可以通过 Ara-C 输注诱导激活。Lrig1+神经干细胞在侧脑室壁中均有观察到。在标记后 1 年，从 Lrig1+神经干细胞中追踪到神经母细胞和神经元。
我们将 Lrig1 鉴定为小鼠脑侧脑室壁中长期神经发生干细胞的标志物。Lrig1 表达揭示了 Lrig1+细胞的两种形态，它们作为长期神经发生干细胞发挥作用。Lrig1+神经干细胞的空间分布表明，所有成年神经干细胞亚型均被标记。
