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

Bruzelius, Andreas LU ; Stamouli, Christina Anastasia LU ; Hölldobler, Anna Lena ; Aretio-Medina, Constanza LU orcid ; Cepeda-Prado, Efrain LU orcid ; Sozzi, Edoardo LU orcid ; Passarello, Germán Ramos LU ; Nocera, Gianluigi LU ; Giacomoni, Jessica LU and Olariu, Victor LU , et al. (2025) In Stem Cell Reports 20(9).
Abstract

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,... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
3D cell culture, astrocytes, disease modelling, GABAergic interneurons, glia precursor, hESC, MGE, neuroscience, patch-clamp electrophysiology, somatostatin
in
Stem Cell Reports
volume
20
issue
9
article number
102634
publisher
Cell Press
external identifiers
  • scopus:105015078609
  • pmid:40930061
ISSN
2213-6711
DOI
10.1016/j.stemcr.2025.102634
language
English
LU publication?
yes
id
ba435447-b816-427b-b3f3-0e695fd43743
date added to LUP
2025-10-15 11:52:58
date last changed
2025-11-12 13:52:42
@article{ba435447-b816-427b-b3f3-0e695fd43743,
  abstract     = {{<p>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.</p>}},
  author       = {{Bruzelius, Andreas and Stamouli, Christina Anastasia and Hölldobler, Anna Lena and Aretio-Medina, Constanza and Cepeda-Prado, Efrain and Sozzi, Edoardo and Passarello, Germán Ramos and Nocera, Gianluigi and Giacomoni, Jessica and Olariu, Victor and Rylander Ottosson, Daniella}},
  issn         = {{2213-6711}},
  keywords     = {{3D cell culture; astrocytes; disease modelling; GABAergic interneurons; glia precursor; hESC; MGE; neuroscience; patch-clamp electrophysiology; somatostatin}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{Three-dimensional co-culturing reveals human stem cell-derived somatostatin interneurons with subclass expression}},
  url          = {{http://dx.doi.org/10.1016/j.stemcr.2025.102634}},
  doi          = {{10.1016/j.stemcr.2025.102634}},
  volume       = {{20}},
  year         = {{2025}},
}