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3D model for human glia conversion into subtype-specific neurons, including dopamine neurons

Giacomoni, Jessica LU ; Bruzelius, Andreas LU ; Habekost, Mette LU orcid ; Kajtez, Janko LU orcid ; Ottosson, Daniella Rylander LU orcid ; Fiorenzano, Alessandro LU ; Storm, Petter LU orcid and Parmar, Malin LU orcid (2024) In Cell reports methods 4(9).
Abstract

Two-dimensional neuronal cultures have a limited ability to recapitulate the in vivo environment of the brain. Here, we introduce a three-dimensional in vitro model for human glia-to-neuron conversion, surpassing the spatial and temporal constrains of two-dimensional cultures. Focused on direct conversion to induced dopamine neurons (iDANs) relevant to Parkinson disease, the model generates functionally mature iDANs in 2 weeks and allows long-term survival. As proof of concept, we use single-nucleus RNA sequencing and molecular lineage tracing during iDAN generation and find that all glial subtypes generate neurons and that conversion relies on the coordinated expression of three neural conversion factors. We also show the formation of... (More)

Two-dimensional neuronal cultures have a limited ability to recapitulate the in vivo environment of the brain. Here, we introduce a three-dimensional in vitro model for human glia-to-neuron conversion, surpassing the spatial and temporal constrains of two-dimensional cultures. Focused on direct conversion to induced dopamine neurons (iDANs) relevant to Parkinson disease, the model generates functionally mature iDANs in 2 weeks and allows long-term survival. As proof of concept, we use single-nucleus RNA sequencing and molecular lineage tracing during iDAN generation and find that all glial subtypes generate neurons and that conversion relies on the coordinated expression of three neural conversion factors. We also show the formation of mature and functional iDANs over time. The model facilitates molecular investigations of the conversion process to enhance understanding of conversion outcomes and offers a system for in vitro reprogramming studies aimed at advancing alternative therapeutic strategies in the diseased brain.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
3D model, CP: neuroscience, CP: stem cell, direct conversion, dopamine release, hGPCs, induced neurons, lineage tracing, neuronal reprogramming, patch-clamp electrophysiology, snRNA sequencing, spheroid
in
Cell reports methods
volume
4
issue
9
article number
100845
publisher
Cell Press
external identifiers
  • pmid:39236715
  • scopus:85204510386
ISSN
2667-2375
DOI
10.1016/j.crmeth.2024.100845
language
English
LU publication?
yes
id
47891532-9f12-48d7-9bfe-70badfa464fa
date added to LUP
2024-11-18 15:47:10
date last changed
2025-07-01 22:02:05
@article{47891532-9f12-48d7-9bfe-70badfa464fa,
  abstract     = {{<p>Two-dimensional neuronal cultures have a limited ability to recapitulate the in vivo environment of the brain. Here, we introduce a three-dimensional in vitro model for human glia-to-neuron conversion, surpassing the spatial and temporal constrains of two-dimensional cultures. Focused on direct conversion to induced dopamine neurons (iDANs) relevant to Parkinson disease, the model generates functionally mature iDANs in 2 weeks and allows long-term survival. As proof of concept, we use single-nucleus RNA sequencing and molecular lineage tracing during iDAN generation and find that all glial subtypes generate neurons and that conversion relies on the coordinated expression of three neural conversion factors. We also show the formation of mature and functional iDANs over time. The model facilitates molecular investigations of the conversion process to enhance understanding of conversion outcomes and offers a system for in vitro reprogramming studies aimed at advancing alternative therapeutic strategies in the diseased brain.</p>}},
  author       = {{Giacomoni, Jessica and Bruzelius, Andreas and Habekost, Mette and Kajtez, Janko and Ottosson, Daniella Rylander and Fiorenzano, Alessandro and Storm, Petter and Parmar, Malin}},
  issn         = {{2667-2375}},
  keywords     = {{3D model; CP: neuroscience; CP: stem cell; direct conversion; dopamine release; hGPCs; induced neurons; lineage tracing; neuronal reprogramming; patch-clamp electrophysiology; snRNA sequencing; spheroid}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{Cell Press}},
  series       = {{Cell reports methods}},
  title        = {{3D model for human glia conversion into subtype-specific neurons, including dopamine neurons}},
  url          = {{http://dx.doi.org/10.1016/j.crmeth.2024.100845}},
  doi          = {{10.1016/j.crmeth.2024.100845}},
  volume       = {{4}},
  year         = {{2024}},
}