98%
921
2 minutes
20
In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate specific neuronal subtypes are still limited. Here, we performed systematic analysis of single-cell genomic data to identify enhancer candidates for each of the telencephalic interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic interneurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP), and manipulate (opto-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.neuron.2025.05.002 | DOI Listing |
Stem Cell Reports
September 2025
Regenerative Neurophysiology, Lund Stem Cell Centre, MultiPark Strategic Area in Neuroscience, Department of Experimental Medical Science, Faculty of Medicine, Lund University, 221 84 Lund, Sweden. Electronic address:
Cortical interneuron deficiencies, particularly involving the somatostatin (SST) subtypes, contribute to neurological and neuropsychiatric disorders. These interneurons are difficult to derive in vitro from human embryonic stem cells (hESCs) due to their late embryonic development and dependence on glial interaction. To this end, we developed a three-dimensional co-culture model of hESC-derived neurons, enabling long-term development, functional maturity, and neuron-glial interaction.
View Article and Find Full Text PDFStructural brain abnormalities in psychosis are well-replicated but heterogenous posing a barrier to uncovering the pathophysiology, etiology, and treatment of psychosis. To parse neurostructural heterogeneity and assess for the presence of anatomically-derived subtypes, we applied a data-driven method, similarity network fusion (SNF), to structural neuroimaging data in a broad cohort of individuals with psychosis (schizophrenia spectrum disorders (SSD) n=280; bipolar disorder with psychotic features (BD) n=101). SNF identified two transdiagnostic subtypes in psychosis (subtype 1: n=158 SSD, n=75 BD; subtype 2: n=122 SSD, n=26 BD) that exhibited divergent patterns of abnormal cortical surface area and subcortical volumes.
View Article and Find Full Text PDFWhile significant progress has been made in understanding the heterogeneity in the NSCs, our understanding of similar heterogeneity among the more abundant transit amplifying progenitors is lagging. Our work on the NPs of the neonatal subventricular zone (SVZ) began over a decade ago, when we used antibodies to the 4 antigens, Lex CD133,LeX,CD140a and NG2 and FACs to classify subsets of the neontal SVZ as either multi-potential (MP1, MP2, MP3, MP4 and PFMPs), glial-restricted (GRP1, GRP2, and GRP3), or neuron-astrocyte restricted (BNAP). Using RNAseq we have characterized the distinctive molecular fingerprint of 4 SVZ neural progenitors and compared their gene expression profiles to those of the NSCs.
View Article and Find Full Text PDFRes Sq
August 2025
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Section on Cellular and Synaptic Physiology, National Institutes of Health (NIH), Bethesda, MD 20892 USA.
The mammalian dentate gyrus contributes to mnemonic function by parsing similar events and places. The disparate activity patterns of mossy cells and granule cells are believed to enable this function yet the mechanisms that drive this circuit dynamic remain elusive. We identified a novel inhibitory interneuron subtype, characterized by VGluT3 expression, with overwhelming target selectivity for mossy cells while also revealing that CCK, PV, SST and VIP interneurons preferentially innervate granule cells.
View Article and Find Full Text PDFCell Death Dis
August 2025
Guangzhou National Laboratory, Guangzhou, 510005, Guangdong, China.
Spinal cord injury (SCI) remains a significant clinical challenge and poses a dramatic threat to the life quality of patients due to limited neural regeneration and detrimental post-injury alternations in tissue microenvironment. We developed a therapeutic approach by transplanting spinal neural progenitor cells (spNPGs), derived from human induced pluripotent stem cell (iPSC)-generated neuromesodermal progenitors, into a contusive SCI model in NOD-SCID mice. Single-cell RNA sequencing mapped the in vitro differentiation of iPSC-spNPGs, confirming their specification into spinal neuronal lineages.
View Article and Find Full Text PDF