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Distinct media requirements for dopaminergic neuron reprogramming from human glia and fibroblasts

Laurin, Kerstin LU orcid ; Kajtez, Janko ; Wickham, Jenny LU orcid ; Parmar, Malin LU orcid and Habekost, Mette LU orcid (2026) In Scientific Reports 16(1).
Abstract

Direct reprogramming of somatic cells into induced dopaminergic neurons (iDANs) is a promising strategy for replacing degenerated dopamine neurons in Parkinson’s disease. One current bottleneck for translation of direct neuronal reprogramming is the low reprogramming efficiency and difficulty to acquire enough tyrosine hydroxylase (TH) positive iDANs. Here we systematically refine the culture conditions used for dopaminergic reprogramming of human stem cell-derived glial progenitor cells (GPCs) and adult dermal fibroblasts (DFs). Starting from a standard reprogramming medium containing base medium, growth factors and small molecules, we systematically compared three base media and removed individual small molecules to determine their... (More)

Direct reprogramming of somatic cells into induced dopaminergic neurons (iDANs) is a promising strategy for replacing degenerated dopamine neurons in Parkinson’s disease. One current bottleneck for translation of direct neuronal reprogramming is the low reprogramming efficiency and difficulty to acquire enough tyrosine hydroxylase (TH) positive iDANs. Here we systematically refine the culture conditions used for dopaminergic reprogramming of human stem cell-derived glial progenitor cells (GPCs) and adult dermal fibroblasts (DFs). Starting from a standard reprogramming medium containing base medium, growth factors and small molecules, we systematically compared three base media and removed individual small molecules to determine their specific contribution to reprogramming outcome. The GPCs and DFs were reprogrammed using established transcription factor-based strategies combined with REST inhibition. We found that the two starting cell types benefited from different culture conditions. For GPCs, B27/Neurobasal medium without small molecules yielded the highest neuronal and TH reprogramming efficiency, whereas DFs yielded the highest efficiencies in N2/DMEM/Neurobasal containing small molecules. Further characterization of the GPC-derived iDANs showed that these cells were functional, expressed key dopaminergic markers, and released dopamine upon stimulation. Together, these findings demonstrate that media composition is a key parameter influencing dopaminergic reprogramming efficiency across starting cell types in vitro.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Culture conditions, Direct fibroblast to neuron reprogramming, Direct glia to neuron reprogramming, Induced dopaminergic neurons, Media composition
in
Scientific Reports
volume
16
issue
1
article number
25696
publisher
Nature Publishing Group
external identifiers
  • pmid:42608437
  • scopus:105047601518
ISSN
2045-2322
DOI
10.1038/s41598-026-66620-z
language
English
LU publication?
yes
id
581228c9-9ddf-474d-91ca-ee7f3c18d6c3
date added to LUP
2026-09-01 16:12:31
date last changed
2026-09-02 03:30:15
@article{581228c9-9ddf-474d-91ca-ee7f3c18d6c3,
  abstract     = {{<p>Direct reprogramming of somatic cells into induced dopaminergic neurons (iDANs) is a promising strategy for replacing degenerated dopamine neurons in Parkinson’s disease. One current bottleneck for translation of direct neuronal reprogramming is the low reprogramming efficiency and difficulty to acquire enough tyrosine hydroxylase (TH) positive iDANs. Here we systematically refine the culture conditions used for dopaminergic reprogramming of human stem cell-derived glial progenitor cells (GPCs) and adult dermal fibroblasts (DFs). Starting from a standard reprogramming medium containing base medium, growth factors and small molecules, we systematically compared three base media and removed individual small molecules to determine their specific contribution to reprogramming outcome. The GPCs and DFs were reprogrammed using established transcription factor-based strategies combined with REST inhibition. We found that the two starting cell types benefited from different culture conditions. For GPCs, B27/Neurobasal medium without small molecules yielded the highest neuronal and TH reprogramming efficiency, whereas DFs yielded the highest efficiencies in N2/DMEM/Neurobasal containing small molecules. Further characterization of the GPC-derived iDANs showed that these cells were functional, expressed key dopaminergic markers, and released dopamine upon stimulation. Together, these findings demonstrate that media composition is a key parameter influencing dopaminergic reprogramming efficiency across starting cell types in vitro.</p>}},
  author       = {{Laurin, Kerstin and Kajtez, Janko and Wickham, Jenny and Parmar, Malin and Habekost, Mette}},
  issn         = {{2045-2322}},
  keywords     = {{Culture conditions; Direct fibroblast to neuron reprogramming; Direct glia to neuron reprogramming; Induced dopaminergic neurons; Media composition}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Distinct media requirements for dopaminergic neuron reprogramming from human glia and fibroblasts}},
  url          = {{http://dx.doi.org/10.1038/s41598-026-66620-z}},
  doi          = {{10.1038/s41598-026-66620-z}},
  volume       = {{16}},
  year         = {{2026}},
}