The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics

Abstract

Norepinephrine (NE) neurons in the locus coeruleus (LC) project widely throughout the central nervous system, playing critical roles in arousal and mood, as well as various components of cognition including attention, learning, and memory. The LC-NE system is also implicated in multiple neurological and neuropsychiatric disorders. Importantly, LC-NE neurons are highly sensitive to degeneration in both Alzheimer's and Parkinson's disease. Despite the clinical importance of the brain region and the prominent role of LC-NE neurons in a variety of brain and behavioral functions, a detailed molecular characterization of the LC is lacking. Here, we used a combination of spatially-resolved transcriptomics and single-nucleus RNA-sequencing to characterize the molecular landscape of the LC region and the transcriptomic profile of LC-NE neurons in the human brain. We provide a freely accessible resource of these data in web-accessible formats.

Expression of substance P, NPY and their Receptors Is Altered in Major Depression

“…Also, it is important to note that the results likely mainly reflect the sum of transcript levels in cell bodies, that could include more than one subpopulation of neurons and could range from a few neurons with high levels to many with low levels. This is clearly shown in the mentioned single-cell studies (Mathys et al, 2019;Weber et al, 2022).…”

“…It is therefore important to try to define, in which population(s) the studied transcripts likely are expressed. For PFC we therefore mainly use data from two single-cell/nuclei studies (Mathys et al, 2019; Nagy et al, 2020); for DRN and LC from Weber et al(Weber et al, 2022) and from our own LCM-seq study on LC. Also, it is important to note that the results likely mainly reflect the sum of transcript levels in cell bodies , that could include more than one subpopulation of neurons and could range from a few neurons with high levels to many with low levels.…”

“…A recent single-nucleus study has reported on 5-HT neurons in the most caudal part of the human DRN (intermingling with NE-LC neurons) (Weber et al, 2022). The results show that the 5-HT neurons are characterized by (i) a robust expression of TAC1 and a modest signal for TACR1 and TACR3 ; (ii) in general very low expression of the NPY family members - only NPYR1 is detected; and (iii) a weak expression of GalR2 and GALR3 , but no signal for GAL or GALR1 .…”

“…The results show that the 5-HT neurons are characterized by (i) a robust expression of TAC1 and a modest signal for TACR1 and TACR3 ; (ii) in general very low expression of the NPY family members - only NPYR1 is detected; and (iii) a weak expression of GalR2 and GALR3 , but no signal for GAL or GALR1 . All transcripts are in addition expressed at various levels in excitatory and inhibitory neurons, as well as in other cell types (Weber et al, 2022).…”

“…However, an unexpected finding is that GalR1 is not only is expressed in NE-LC cells (at modest levels) but mainly and robustly in oligodendrocyte precursor cells (Weber et al, 2022). All transcripts are in addition expressed at various levels in excitatory and inhibitory neurons and often in other cell types (Weber et al, 2022).…”