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Mutations in GFAP Alter Early Lineage Commitment of Organoids

Dykstra, Werner ; Matusova, Zuzana ; Battaglia, Rachel A ; Abaffy, Pavel ; Goya-Iglesias, Nuria ; Pérez-Sala, Dolores ; Ahlenius, Henrik LU ; Kubista, Mikael ; Pasterkamp, R Jeroen and Li, Li , et al. (2025) In GLIA p.1-22
Abstract

Glial fibrillary acidic protein (GFAP) is a type-3 intermediate filament protein mainly expressed in astrocytes in the central nervous system. Mutations in GFAP cause Alexander disease (AxD), a rare and fatal neurological disorder. How exactly mutant GFAP eventually leads to white and gray matter deterioration in AxD remains unknown. GFAP is known to be expressed also in neural precursor cells in the developing brain. Here, we used AxD patient-derived induced pluripotent stem cells (iPSCs) to explore the impact of mutant GFAP during neurodifferentiation. Our results show that GFAP is already expressed in iPSCs. Moreover, we have found that mutations in GFAP can severely affect neural organoid development through altering lineage... (More)

Glial fibrillary acidic protein (GFAP) is a type-3 intermediate filament protein mainly expressed in astrocytes in the central nervous system. Mutations in GFAP cause Alexander disease (AxD), a rare and fatal neurological disorder. How exactly mutant GFAP eventually leads to white and gray matter deterioration in AxD remains unknown. GFAP is known to be expressed also in neural precursor cells in the developing brain. Here, we used AxD patient-derived induced pluripotent stem cells (iPSCs) to explore the impact of mutant GFAP during neurodifferentiation. Our results show that GFAP is already expressed in iPSCs. Moreover, we have found that mutations in GFAP can severely affect neural organoid development through altering lineage commitment in embryoid bodies. Together, these results support the notion that GFAP plays a role as an early modulator of neurodevelopment.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
GLIA
pages
1 - 22
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:40735838
ISSN
1098-1136
DOI
10.1002/glia.70049
language
English
LU publication?
yes
additional info
© 2025 The Author(s). GLIA published by Wiley Periodicals LLC.
id
9b86a7f5-131a-47cb-af7f-30067b2f36eb
date added to LUP
2025-08-26 11:04:00
date last changed
2025-08-26 12:00:33
@article{9b86a7f5-131a-47cb-af7f-30067b2f36eb,
  abstract     = {{<p>Glial fibrillary acidic protein (GFAP) is a type-3 intermediate filament protein mainly expressed in astrocytes in the central nervous system. Mutations in GFAP cause Alexander disease (AxD), a rare and fatal neurological disorder. How exactly mutant GFAP eventually leads to white and gray matter deterioration in AxD remains unknown. GFAP is known to be expressed also in neural precursor cells in the developing brain. Here, we used AxD patient-derived induced pluripotent stem cells (iPSCs) to explore the impact of mutant GFAP during neurodifferentiation. Our results show that GFAP is already expressed in iPSCs. Moreover, we have found that mutations in GFAP can severely affect neural organoid development through altering lineage commitment in embryoid bodies. Together, these results support the notion that GFAP plays a role as an early modulator of neurodevelopment.</p>}},
  author       = {{Dykstra, Werner and Matusova, Zuzana and Battaglia, Rachel A and Abaffy, Pavel and Goya-Iglesias, Nuria and Pérez-Sala, Dolores and Ahlenius, Henrik and Kubista, Mikael and Pasterkamp, R Jeroen and Li, Li and Chao, Jianfei and Shi, Yanhong and Valihrach, Lukas and Pekny, Milos and Hol, Elly M}},
  issn         = {{1098-1136}},
  language     = {{eng}},
  month        = {{07}},
  pages        = {{1--22}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{GLIA}},
  title        = {{Mutations in GFAP Alter Early Lineage Commitment of Organoids}},
  url          = {{http://dx.doi.org/10.1002/glia.70049}},
  doi          = {{10.1002/glia.70049}},
  year         = {{2025}},
}