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Three-dimensional co-culturing reveals human stem cell-derived somatostatin interneurons with subclass expression.

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.

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Structural 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.

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While 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.

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A novel and evolutionarily conserved inhibitory circuit selectively regulates dentate gyrus mossy cell function.

Res 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.

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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.

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