Transcriptional regulation of neural stem cell expansion in adult hippocampus

Nannan Guo, Kelsey D. McDermott, Yu Tzu Shih, Haley Zanga, Debolina Ghosh, Charlotte Herber, William R. Meara, James Coleman, Alexia Zagouras, Lai Ping Wong, Ruslan Sadreyev, J. Tiago Gonçalves, Amar Sahay

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere72195
JournaleLife
Volume11
DOIs
StatePublished - Jan 2022

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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