Hepatoma Derived Growth Factor Enhances Oligodendrocyte Genesis from Subventricular Zone Precursor Cells

Abstract

Oligodendrocytes, the myelinating cells of the central nervous system (CNS), perform vital functions in neural protection and communication, as well as cognition. Enhanced production of oligodendrocytes has been identified as a therapeutic approach for neurodegenerative and neurodevelopmental disorders. In the postnatal brain, oligodendrocytes are generated from the neural stem and precursor cells (NPCs) in the subventricular zone (SVZ) and parenchymal oligodendrocyte precursor cells (OPCs). Here, we demonstrate exogenous Hepatoma Derived Growth Factor (HDGF) enhances oligodendrocyte genesis from murine postnatal SVZ NPCs in vitro without affecting neurogenesis or astrogliogenesis. We further show that this is achieved by increasing proliferation of both NPCs and OPCs, as well as OPC differentiation into oligodendrocytes. In vivo results demonstrate that intracerebroventricular infusion of HDGF leads to increased oligodendrocyte genesis from SVZ NPCs, as well as OPC proliferation. Our results demonstrate a novel role for HDGF in regulating SVZ precursor cell proliferation and oligodendrocyte differentiation. Summary Statement Hepatoma derived growth factor (HDGF) is produced by neurons. However, its role in the central nervous system is largely unknown. We demonstrate HDGF enhances i) oligodendrocyte formation from subventricular zone neural stem cells, and ii) oligodendrocyte precursor proliferation in vitro and in vivo.

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“…Sections were processed as described in (de Almeida et al, 2023;Li et al, 2022;Watson et al, 2021). Briefly, sections were dried at 37ºC, washed with phosphate buffered saline (PBS), and blocked for 1 hour (5% bovine serum albumin [BSA, Jackson ImmunoResearch, 001-000-162], 0.3% Triton-X100 in PBS), then incubated with primary antibodies listed in "Reagents" section (in 5% BSA) overnight at 4°C.…”

Olfactory bulb anomalies in KBG syndrome mouse model and patients

“…To determine the role of Ankrd11 in OB development, we induced knockout of Ankrd11 in embyronic day (E) 14.5 NPCs and their subsequent progeny by breeding Ankrd11 fl/ fl mice, where exon 7 of the Ankrd11 gene is flanked by loxP sites, with TMX-inducible NestinCre ERT2 recombinase that is expressed specifically in Nestin + NPCs (Fig. 1A) [61][62][63]. Upon TMX administration, Cre causes recombination at the floxed exon 7 of Ankrd11 in NPCs, creating a frameshift mutation that encompasses all known functional domains of the protein [58,59].…”

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“…Staining with FluoroMyelin was performed as per manufacturer’s instructions (Invitrogen). For all other staining, sections were stained as described in Li et al. (2022) and Watson et al.…”