Differential Hes1 activation defines neural stem cell lineage commitment and niche maintenance in embryonic and adult mouse cortex

• 成果类型: Article
• 署名作者: Riya, Paul Ann; Jose, Rahul; Meera, Vadakkath; Basu, Budhaditya; Surya, Suresh; Aryasree, Ramankunju; Jyothi, Nair Pradeep; Parvathy, Surendran; Dhanesh, Sivadasan Bindu; Sanalkumar, Rajendran; Praz, Viviane; Riggi, Nicolo; James, Jackson
• 署名单位: Department of Biotechnology (DBT) India; Rajiv Gandhi Centre for Biotechnology (RGCB); University of Kerala; Department of Biotechnology (DBT) India; Regional Centre for Biotechnology; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Johns Hopkins University; University of Iowa; Stanford Medicine; Stanford University; Children's Mercy Hospital; Roche Holding; Roche Holding USA; Genentech
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2511800123
• 发表日期: 2026-01-27
• 页码: e2511800123
• 关键词: Notch-independent Hes1; neural stem cells; cortical development; radial glial cells; notch signaling; radial glia; HES GENES; differentiation; roles; protein; specification; neurogenesis; expression; promote; neurons

摘要

Mode of Hes1 activation and its differential expression are crucial for the maintenance of neural stem cells/progenitor cells (NSCs/NPCs) in the embryonic cortex. This differential mode of Hes1 activation has been translated into a heterogeneous population of NSCs comprising Notch-independent Hes1-expressing (NIHes1) NSCs and Notch-dependent Hes1-expressing (NDHes1) radial glial cells (RGCs). Using single-cell transcriptomics and a Nestin-CreERT2;NIHes1fl/fl conditional knock-out mouse model, we have characterized the NIHes1 NSCs. Our analyses show that NIHes1 NSCs are the ancestral precursor NSCs that generate RGCs and intermediate progenitor cells during development. Loss of NIHes1 expression significantly alters the NSC niche, leading to increased gliogenesis and aberrant migration of projection neurons. NIHes1 NSCs are set aside at embryonic stages as adult neural stem cells and are maintained by NIHes1 expression even at adult stage. Our findings suggest that NIHes1 NSCs are functionally distinct Hes1-expressing NSCs, which are critical for establishing both embryonic and adult NSC niches, thereby contributing to the overall cortical development.