Biology subjects

Giger, R.

Publications and source records attributed to Giger, R..

3 recordsLinked to original sources

bioRxiv2025

AxoMetric: A Rapid and Unbiased Tool for Automated Quantification of Axon Regeneration in Tissue Sections

Recent advances in experimental strategies that promote axon regeneration in adult mammals lay the foundation for future therapies. Reliable and unbiased quantification of regenerated axons is challenging, yet essential for comparing the efficacy of individual treatments and identification of most efficacious combinatorial therapies. Here, we introduce AxoMetric, a user-friendly and freely available software for the rapid quantification of regenerated axons in longitudinal nerve tissue sections. AxoMetric automatically identifies and traces regenerated axons, generating quantitative measurements that closely match conventional manual quantification but with significantly greater speed. Key features include length-dependent axon quantification at defined intervals from the injury site and normalization of axon density to nerve diameter to account for anatomical variability. To facilitate high-throughput analysis, the software includes an image queuing function. Additional features of AxoMetric allow quantification of a range of labeled cellular structures. As a proof of concept, we demonstrate accurate quantification of regenerated axons in the optic nerve, retinal ganglion cells density in retinal flat-mounts, and regenerated axon bundles in injured sciatic nerves. Collectively, we introduce a new platform that is expected to streamline and standardize regenerative outcome assessments across diverse experimental conditions and laboratories. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/662816v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@162d692org.highwire.dtl.DTLVardef@1f52ed4org.highwire.dtl.DTLVardef@1d58f76org.highwire.dtl.DTLVardef@1bdabb1_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Coordinated differentiation of human intestinal organoids with functional enteric neurons and vasculature

Human intestinal organoids (HIOs) derived from human pluripotent stem cells co-differentiate both epithelial and mesenchymal lineages in vitro but lack important cell types such as neurons, endothelial cells, and smooth muscle. Here, we report an in vitro method to derive HIOs with epithelium, mesenchyme, enteric neuroglial populations, endothelial cells, and organized smooth muscle in a single differentiation, without the need for co-culture. When transplanted into a murine host, these populations expand and organize to support organoid maturation and function. Functional experiments demonstrate enteric nervous system function, with HIOs undergoing peristaltic-like contractions, suggesting the development of a functional neuromuscular unit. HIOs also form functional vasculature, demonstrated in vitro using microfluidic devices to introduce vascular-like flow, and in vivo following transplantation, where HIO endothelial cells anastomose with host vasculature. Collectively, we report an in vitro model of the human gut that simultaneously co-differentiates epithelial, stromal, endothelial, neural, and organized muscle populations.

bioengineering↗

bioRxiv2020

THAP1 Modulates Oligodendrocyte Maturationby Regulating ECM Degradation in Lysosomes

Mechanisms controlling myelination during CNS maturation play a pivotal role in the development and refinement of CNS circuits. The transcription factor THAP1 is essential for timing the inception of myelination during CNS maturation through a cell-autonomous role in the oligodendrocyte lineage. Here, we demonstrate that THAP1 modulates ECM composition by regulating glycosaminoglycan (GAG) catabolism within oligodendrocyte progenitor cells (OPCs). Thap1-/- OPCs accumulate and secrete excess GAGs, inhibiting their maturation through an auto-inhibitory mechanism. THAP1 controls GAG metabolism by binding to and regulating the GusB gene encoding {beta}-glucuronidase, a GAG-catabolic lysosomal enzyme. Applying GAG-degrading enzymes or overexpressing {beta}-glucuronidase rescues Thap1-/- OL maturation deficits in vitro and in vivo. Our studies establish lysosomal GAG catabolism within OPCs as a critical mechanism regulating oligodendrocyte development.

neuroscience↗