Université Paris Cité, Inserm, CEA, Stabilité Génétique Cellules Souches et Radiations, LRP/iRCM, Fontenay-aux-Roses, France.
Université Paris-Saclay, Inserm, CEA, Stabilité Génétique Cellules Souches et Radiations, LRP/iRCM, Fontenay-aux-Roses, France.
Elife. 2024 Nov 22;12:RP87083. doi: 10.7554/eLife.87083.
The lateral wall of the mouse subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single-cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into two subtypes, iNB1 and iNB2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage.
小鼠侧脑室壁含有神经干细胞（NSC，B 细胞），它们产生增殖的短暂扩增祖细胞（TAP，C 细胞），最终产生神经母细胞（NB，A 细胞）。单细胞水平的分子谱分析难以区分这些不同的细胞类型。在这里，我们结合了 FACS 分选细胞的转录组分析和单细胞 RNAseq，证明了在 TAP 和迁移 NB（mNB）之间的过渡中存在丰富的、克隆性的和多能的未成熟神经母细胞（iNB 细胞）群体。iNB 可逆地参与神经元分化。事实上，它们保持了未分化祖细胞、可塑性和意外的再生特性的分子特征。引人注目的是，它们经历了重要的渐进性分子转换，包括剪接调节因子表达的变化，导致它们在 mNB 中分化，将其分为两个亚型，iNB1 和 iNB2。由于其可塑性，iNB 可能成为脑损伤再生治疗的新靶点。
