Reconsidering Neurogenetic Indication in the Human Brain: Broad Expression of Doublecortin Transcript in the Hippocampal and Cortical Cell Populations

Cells Tissues Organs. 2024;213(5):382-389. doi: 10.1159/000540976. Epub 2024 Aug 27.

Abstract

Introduction: Neurogenesis in the adult brain may play an important role in memory and cognition; however, knowledge of neurogenic markers in the human brain remains limited. We compared the single-nucleus transcriptome of the hippocampus with that of other cortical regions to identify hippocampus-specific neurogenic markers.

Methods: We analyzed 26,189 nuclei from four human brains collected within 16 h of death. Clustering and annotation were performed to examine differential expression, gene ontology, and intercellular communication. DCX expression was validated by ddPCR.

Results: Immature markers such as DCX, CALB2, NES, SOX2, PAX6, DPYSL3, and TUBB3 were expressed in both hippocampus and prefrontal cortex, with higher levels in the prefrontal cortex. ddPCR confirmed higher expression of DCX in the prefrontal cortex. DCX was involved in both neurogenesis and neuroprotection pathways.

Conclusion: Neurogenic markers are not definitive indicators of adult neurogenesis as their roles are more complex than previously understood.

Keywords: Adult neurogenesis; Degenerative disease; Hippocampus; Neural stem cell; Prefrontal cortex; Single-nucleus RNA sequencing.

Publication types

  • News

MeSH terms

  • Adult
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Doublecortin Domain Proteins
  • Doublecortin Protein* / metabolism
  • Female
  • Hippocampus* / metabolism
  • Humans
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Neurogenesis*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Transcriptome

Substances

  • DCX protein, human
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neuropeptides

Grants and funding

This study was financially supported by the “Hankookilbo Myung-Ho Seung” Faculty Research Assistance Program of Yonsei University College of Medicine (6-2022-0069). This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. RS-2023-00246638). This research was supported by the Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea (to H.-M.Y.). This study was funded by the National Research Foundation of Korea (NRF), funded by the Korean government (NRF-2021R1A2C2008034).