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Biology subjects

Lu, T.-Y.

Publications and source records attributed to Lu, T.-Y..

2 recordsLinked to original sources

Norepinephrine enhances oligodendrocyte precursor cell calcium dynamics in the cerebral cortex during arousal

Oligodendrocytes are generated from a widely distributed population of progenitors that express neurotransmitter receptors, but the mechanisms that alter activity of these oligodendrocyte precursor cells (OPCs) in vivo have not been determined. We generated a novel line of transgenic mice to express membrane-anchored GCaMP6s in OPCs and used longitudinal two-photon microscopy to monitor their Ca2+ changes in the cerebral cortex of awake mice. OPCs exhibited high rates of spontaneous activity, consisting of focal, transient Ca2+ increases within their highly ramified processes. Unexpectedly, these events occurred independent of excitatory neuron activity, but were inhibited by anesthesia, sedative agents, and antagonists of noradrenergic signaling. These norepinephrine enhanced Ca2+ dynamics rapidly declined as with differentiation. Selective knockout of 1A adrenergic receptors in OPCs suppressed both spontaneous and locomotion-induced Ca2+ increases, indicating that OPCs are directly modulated by norepinephrine in vivo, providing a means to alter their dynamics and lineage progression during distinct brain states.

neuroscience↗

A Draft Human Pangenome Reference

The Human Pangenome Reference Consortium (HPRC) presents a first draft human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence and are more than 99% accurate at the structural and base-pair levels. Based on alignments of the assemblies, we generated a draft pangenome that captures known variants and haplotypes, reveals novel alleles at structurally complex loci, and adds 119 million base pairs of euchromatic polymorphic sequence and 1,529 gene duplications relative to the existing reference, GRCh38. Roughly 90 million of the additional base pairs derive from structural variation. Using our draft pangenome to analyze short-read data reduces errors when discovering small variants by 34% and boosts the detected structural variants per haplotype by 104% compared to GRCh38-based workflows, and by 34% compared to using previous diversity sets of genome assemblies.

genomics↗