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Senior Lecturer Victor Olariu, MSc, PhD. Photo

Victor Olariu

Senior lecturer

Senior Lecturer Victor Olariu, MSc, PhD. Photo

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

Author

  • Andreas Bruzelius
  • Christina Anastasia Stamouli
  • Anna Lena Hölldobler
  • Constanza Aretio-Medina
  • Efrain Cepeda-Prado
  • Edoardo Sozzi
  • Germán Ramos Passarello
  • Gianluigi Nocera
  • Jessica Giacomoni
  • Victor Olariu
  • Daniella Rylander Ottosson
Show all

Summary, in English

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. Under these conditions, hESCs successfully differentiated into functional GABAergic interneurons expressing the SST gene and protein within 50 days. Single-nuclei RNA sequencing revealed transcripts for SST subclasses, including Martinotti, non-Martinotti, and long-projecting neurons, that have not yet been described for hESC cultures. Upon injection into forebrain organoids, the interneuron progenitors spread and functionally matured while retaining their SST subclass identities, suggesting cell-intrinsic fate specification. Our in vitro model provides a robust platform for studying human SST interneurons, offering new avenues for investigating their role in health and disease.

Department/s

  • Regenerative Neurophysiology
  • Developmental and Regenerative Neurobiology
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • MultiPark: Multidisciplinary research on neurodegenerative diseases
  • Computational Science for Health and Environment
  • Centre for Environmental and Climate Science (CEC)

Publishing year

2025-09

Language

English

Publication/Series

Stem Cell Reports

Volume

20

Issue

9

Document type

Journal article

Publisher

Cell Press

Topic

  • Neurosciences

Keywords

  • 3D cell culture
  • astrocytes
  • disease modelling
  • GABAergic interneurons
  • glia precursor
  • hESC
  • MGE
  • neuroscience
  • patch-clamp electrophysiology
  • somatostatin

Status

Published

Research group

  • Regenerative Neurophysiology
  • Developmental and Regenerative Neurobiology
  • Computational Science for Health and Environment

ISBN/ISSN/Other

  • ISSN: 2213-6711