biostudies-literatureRiya PADepartment of Science and Technology, Ministry of Science and Technology, IndiaDepartment of Science and Technology, Ministry of Science and Technology, India (DST)e2511800123https://www.ebi.ac.uk/biostudies/studies/S-EPMC12849698biostudies-literatureUnknown123(4)Mode of <i>Hes1</i> 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 <i>Hes1</i> activation has been translated into a heterogeneous population of NSCs comprising Notch-independent <i>Hes1-</i>expressing (NIHes1) NSCs and Notch-dependent <i>Hes1-</i>expressing (NDHes1) radial glial cells (RGCs). Using single-cell transcriptomics and a Nestin-CreERT2;NIHes1^fl/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 Proceedings of the National Academy of Sciences of the United States of AmericaDifferential <i>Hes1</i> activation defines neural stem cell lineage commitment and niche maintenance in embryonic and adult mouse cortex.PMC12849698CRG/2021/005847Surya SRiggi NJyothi NPPraz VDhanesh SBParvathy SJames JMeera VBasu BSanalkumar RJose RRiya PAAryasree RfalseDifferential <i>Hes1</i> activation defines neural stem cell lineage commitment and niche maintenance in embryonic and adult mouse cortex.Mode of <i>Hes1</i> 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 <i>Hes1</i> activation has been translated into a heterogeneous population of NSCs comprising Notch-independent <i>Hes1-</i>expressing (NIHes1) NSCs and Notch-dependent <i>Hes1-</i>expressing (NDHes1) radial glial cells (RGCs). Using single-cell transcriptomics and a Nestin-CreERT2;NIHes1^fl/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 2026-01-01T00:00:00Z2026 Jan2026-06-16T07:10:14.439Z2026-06-16T03:10:00.602ZS-EPMC128496984155779010.1073/pnas.2511800123