Search bioRxiv⌕ Search

Biology subjects

Brogger, P.

Publications and source records attributed to Brogger, P..

2 recordsLinked to original sources
bioRxiv2025

Histone hyperacetylation-linked upregulation of KRAB zinc finger proteins impedes glial differentiation in Huntington's disease

Glial differentiation is impaired in Huntington disease (HD), contributing to both the synaptic dysfunction and hypomyelination of HD. Through combined epigenomic and transcriptomic profiling, we found that glial progenitor cells (hGPCs) generated from HD-derived human embryonic stem cells exhibit persistent histone hyperacetylation, enabling the ectopic expression of a broad set of KRAB zinc finger protein (KZFP) transcriptional repressors. Single-cell RNA-Seq analysis of HD hGPCs revealed that their aberrant KZFP expression was attended by the persistent expression of neural progenitor-stage genes relative to wild-type hGPCs. The HD hGPCs over-expressed the MYST family histone acetyltransferase KAT6B, which led to their hyperacetylation at H3K9 and associated DNA demethylation, and displayed abnormally open chromatin, particularly at promoters of chromosome 19 KZFP gene clusters. Among those KZFPs most differentially activated in HD hGPCs was the primate-specific ZNF98, whose overexpression in wild-type hGPCs recapitulated the HD-associated suppression of glial development. These data implicate abnormal histone hyperacetylation in HD glial progenitor cells, and its associated over-expression of recently evolved KZFP transcriptional repressors, as a critical mechanism by which both astrocytic and oligodendrocytic differentiation are impaired in HD.

neuroscience↗
bioRxiv2022

Liver-secreted fluorescent blood plasma markers enable chronic imaging of microcirculation

Studying blood microcirculation is vital for gaining insights into vascular diseases. Acute administration of fluorescent tracers is currently used for deep tissue blood flow imaging. This is invasive, and the plasma fluorescence decreases within an hour of administration. We report a novel approach for the longitudinal study of vasculature. Using a single systemic administration of viral vectors, we express fluorescent secretory albumin-fusion proteins in the liver to label the blood in mice. All segments of the vasculature in brain and peripheral tissue are observable by two-photon microscopy within two weeks of vector administration. This approach allows for observation of circulation without the need for repeated administration for several months. We demonstrate the chronic assessment of vascular functions at micro-and mesoscopic scales. This genetic plasma labeling approach represents a versatile and cost-effective method for the chronic investigation of vasculature functions across the body in health and disease.

physiology↗