Molecular diversity among adult hippocampal and entorhinal cells

doctoral thesis

• Author: Daniel Franjić
• Mentor: Goran Sedmak (mentor)
• Mentor: Nenad Šestan (komentor); VIAF: 316026737
• Committee member: Goran Šimić (predsjednik povjerenstva)
• Committee member: Mario Vukšić (član povjerenstva)
• Committee member: Dubravka Hranilović (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Croatian Institiute for Brain Research); Zagreb
• Defense date and country: 2025-01-03, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

The hippocampal system is a critical component in cognition, adult neurogenesis, and selectively sensitive to aging and neurodegenerative processes. To gain insights into neurogenic potential and diversity of cell types in adult humans, we profiled single-nucleus transcriptomes in five hippocampal subregions. Integration of dentate gyrus data with mouse, pig and macaque, showed strong neurogenesis trajectories in these species that was absent in humans. Doublecortin (DCX), the common marker of neurogenesis in the dentate gyrus, showed widespread expression in the human hippocampal system, including some mature
dentate granule cells, but did not define immature cell populations in humans. We further revealed prominent diversity among excitatory neurons across the hippocampal system that echoed the transition from three-layered archicortex to six-layered neocortex. Our results highlighted the uncharacterized METTL7B associated with Alzheimer’s disease-related proteins and enriched in primates in neuronal subtypes and subregions more resilient to early neuropathological changes in the Alzheimer’s disease. Overall, our findings unveiled cell typespecific molecular characteristics pertinent to hippocampal physiological function.

Abstract (croatian)

Neuralni krugovi hipokampalne (HIP) i entorinalne moždane kore (EC) ključni su dijelovi široke neuronske mreže odgovorne za pamćenje te reprezentaciju prostora i vremena. U svrhu boljeg uvida u pojedinačne neuronske i ne-neuronske populacije tog sustava, provedeno je RNA sekvencioniranje pojedinačnih staničnih jezgara (snRNA-seq) uzoraka iz pet anatomski definiranih podregija hipokampalnog sustava. Integrirana analiza između vrsta pokazala je transkriptomske i histološke znakove neurogeneze u odraslim miševima, svinjama i makaki majmunima, ali ne i u ljudi. DCX, marker novonastalih zrnatih stanica, pronađen je u različitim neuronskim populacijama odraslog čovjeka, ali nije definirao populacije nezrelih neurona. Također, opisali smo specifične, subregionalno transkriptomski definirane tipove stanica i promjene u prijelazu iz troslojnog arhikorteksa u šestoslojni neokorteks. Naši rezultati istaknuli su da je METTL7B povezan s proteinima povezanim s Alzheimerovom bolešću i obogaćen u primata u podtipovima stanica i podregijama otpornijim na rane neuropatološke promjene u Alzheimerovoj bolesti. Ovo istraživanje je otkrilo molekularne karakteristike određenih vrsta i podtipova stanica koje potencijalno imaju važnu ulogu u fiziološkoj funkciji i/ili patološkim promjenama hipokampalnog sustava.

• Keywords: Single-cell; RNA-seq; hippocampus; entorhinal cortex; evolution; adult neurogenesis; neocortex; aging
• Keywords (english): RNA-sekvenciranje pojedinačnih stanica; hipokampus; entorinalna moždana kora; evolucija; neurogeneza u odrasloj dobi; neokorteks; starenje
• Language: english
• URN:NBN: urn:nbn:hr:105:053196
• Study programme: Title: Neuroscience; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 159 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-01-24 09:23:40