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Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17

ABSTRACT: Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17

PROVIDER: PRJNA813346 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18250000.fastq.gz	Fastqsanger.gz
	SRR18250001.fastq.gz	Fastqsanger.gz
	SRR18250002.fastq.gz	Fastqsanger.gz
	SRR18250003.fastq.gz	Fastqsanger.gz
	SRR18250004.fastq.gz	Fastqsanger.gz

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Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17

Project description:Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.

2022-05-11 | GSE198008 | GEO

Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17.

Project description: Not available

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Patterning effects of FGF17 and cAMP on generation of dopaminergic progenitors for cell replacement therapy in Parkinson’s disease. [scRNA-Seq]

Project description:Cell replacement therapies using human pluripotent stem cell-derived dopaminergic (DA) progenitors are currently in clinical trials for treatment of Parkinson’s disease (PD). Recapitulating developmental patterning cues, such as fibroblast growth factor 8 (FGF8), secreted at the midbrain-hindbrain boundary (MHB), is critical for the in-vitro production of authentic midbrain DA progenitors. Here, we explore the application of alternative MHB-secreted FGF-family members, FGF17 and FGF18, for DA progenitor patterning. We show that while FGF17 and FGF18 both recapitulate DA progenitor patterning events, FGF17 induced expression of key DA progenitor markers at higher levels than FGF8 and transplanted FGF17-patterned progenitors fully reversed motor deficits in a rat PD model. Early activation of the cAMP pathway mimicked FGF17-induced patterning, although strong cAMP activation also came at the expense of EN1 expression. In summary, we identified FGF17 as a promising candidate for more precise and robust DA progenitor patterning, with potential to improve cell products for treatment of PD.

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Patterning effects of FGF17 and cAMP on generation of dopaminergic progenitors for cell replacement therapy in Parkinson’s disease. [RNA-Seq]

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Transcriptome analysis of sham-operated, MI-injured and FGF17-treated MI mice hearts (Normal)

Project description:This study investigated whether FGF17 signaling exerts cardioprotective effects in un-injured normal mice hearts.

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Transcriptome analysis of sham-operated, MI-injured and FGF17-treated MI mice hearts (MI)

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Environmental enrichment restores a young DNA methylation landscape in the aged mouse hippocampus

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GM-CSF Production by Non-Classical Monocytes Controls Antagonistic LPS-driven Functions In Allergic Inflammation

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