Biology subjects

Artioli, A.

Publications and source records attributed to Artioli, A..

4 recordsLinked to original sources

bioRxiv2026

A defined 2D system for generating and expanding human basal radial glia from iPSCs

Basal radial glia (bRG) drive human cortical expansion but remain underrepresented in vitro. We established a defined and expandable 2D system for efficient generation of human bRG from iPSCs. These cells recapitulate canonical molecular signatures, hallmark somal translocation behaviours, intrinsic differentiation potential, and integration into organoid tissue. Network-based analyses identified PAK2 as a regulator of mitotic somal translocation, illustrating the systems utility for mechanistic interrogation of bRG biology.

neuroscience↗

bioRxiv2026

Serotonergic innervation and cortical progenitor regulation in human brain assembloids

Neuromodulatory signaling is classically associated with mature neural circuits, yet serotonergic projections reach the developing cortex prior to circuit formation, suggesting a role in early human cortical development. Here, we establish a human raphe-cortical assembloid platform by generating iPSC-derived hindbrain-patterned raphe organoids that produce serotonergic neurons and form projections into fused cortical organoids, exhibiting endogenous serotonin release within developing cortical tissue. Using this system, we find that serotonergic innervation is associated with a shift toward progenitor-enriched states, accompanied by increased proliferative activity, activation of developmental transcriptional programs, and predicted signaling interactions targeting cortical progenitors and neurons. Consistent with these findings, cortical regions receiving serotonergic projections exhibit increased mitotic activity, and pharmacological modulation demonstrates selective proliferative responses in basal progenitor populations, consistent with observations in human fetal tissue. Together, this system provides a framework to investigate how early neuromodulatory input shapes human cortical development and developmental vulnerability.

neuroscience↗

bioRxiv2025

Two independent translocation modes drive neural stem cell dissemination into the human fetal cortex

The strong size increase of the human neocortex is supported both by the amplification and the basal translocation of a neural stem cell population, the basal radial glial cells (or bRG cells). Using live imaging of second trimester human fetal tissue and cortical organoids, we identify two independent translocation modes for bRG cell colonization of the human neocortex. On top of an actomyosin-dependent movement called mitotic somal translocation (MST), we identify a microtubule-dependent motion occurring during interphase, that we call interphasic somal translocation (IST). We show that IST is driven by the LINC complex, through the nuclear envelope recruitment of the dynein motor and of its activator LIS1. Consequently, IST severely altered in LIS1 patient-derived cortical organoids. We also demonstrate that MST occurs during prometaphase and is a mitotic spindle translocation event. MST is controlled by the mitotic cell rounding molecular pathway, via Moesin and Vimentin, driving translocation. We report that 85% of bRG cell translocation is due to IST, for a total movement of 0,67 mm per month of human fetal gestation. Our work identifies how bRG cells colonize the human fetal cortex, and further shows that IST and MST are conserved in bRG-related migrating glioblastoma cells.

neuroscience↗

bioRxiv2024

A multi-omics and cell type-specific characterization of the ventral striatum in human cocaine use disorder

Epigenome, transcriptome, and proteome analyses of postmortem brains have revealed initial molecular insights into cocaine use disorder (CUD). However, the inter-relationship between these -omics and the contribution of individual cell types remain largely unknown. We present an in-depth analysis of molecular changes in the ventral striatum in CUD at multi-omics and single-cell resolution. Integrative multi-omics analyses of microRNA-seq, RNA-seq, and proteomics datasets in 41 individuals and single-nuclei RNA-seq in a subset of 16 individuals revealed conserved deregulation of metabolic pathways, oxidative phosphorylation, and glutamatergic signaling. Cell type-specific analyses identified inverse metabolic pathway deregulation patterns in glial and neuronal cells, notably in astrocytes and medium spiny neurons (MSNs). Characterizing astrocyte-neuron crosstalk revealed altered glutamatergic and cell adhesion signaling in CUD. By applying a comprehensive multi-omics analytical framework, our study provides novel insights into CUD-associated molecular changes in the ventral striatum, suggesting astrocytes, MSNs, and their crosstalk as particularly perturbed in CUD.

neuroscience↗