Experience governs neurogenesis from radial-glial neural stem cells (RGLs) in the adult hippocampus to support memory. Transcription factors in RGLs integrate physiological signals to dictate self-renewal division mode. Whereas asymmetric RGL divisions drive neurogenesis during favorable conditions, symmetric divisions prevent premature neurogenesis while amplifying RGLs to anticipate future neurogenic demands. The identities of transcription factors regulating RGL symmetric self-renewal, unlike those that regulate RGL asymmetric self-renewal, are not known. Here, we show in mice that the transcription factor Kruppel-like factor 9 (Klf9) is elevated in quiescent RGLs and inducible, deletion of Klf9 promotes RGL activation state. Clonal analysis and longitudinal intravital 2-photon imaging directly demonstrate that Klf9 functions as a brake on RGL symmetric self-renewal. In vivo translational profiling of RGLs lacking Klf9 generated a molecular blueprint for RGL symmetric self-renewal that was characterized by upregulation of genetic programs underlying Notch and mitogen signaling, cell-cycle, fatty acid oxidation and lipogenesis. Together, these observations identify Klf9 as a transcriptional regulator of neural stem cell expansion in the adult hippocampus.
Sequencing data have been deposited in GEO under accession code GSE164889.
Transcriptional regulation of neural stem cell expansion in adult hippocampusNCBI Gene Expression Omnibus, GSE164889.
- J Tiago Gonçalves
- Amar Sahay
Animal experimentation: Animals were handled and experiments were conducted in accordance with procedures approved by the Institutional Animal Care and Use Committee (IACUC) at the Massachusetts General Hospital (2011N000084 ) and Albert Einstein College of Medicine in accordance with NIH guidelines.
- Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States
- Received: July 14, 2021
- Accepted: January 3, 2022
- Accepted Manuscript published: January 4, 2022 (version 1)
© 2022, Guo et al.
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