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Mutations in GFAP Alter Early Lineage Commitment of Organoids.

Werner Dykstra | Zuzana Matusova | Rachel A Battaglia | Pavel Abaffy | Nuria Goya-Iglesias | Dolores Pérez-Sala | Henrik Ahlenius | Mikael Kubista | R Jeroen Pasterkamp | Li Li | Jianfei Chao | Yanhong Shi | Lukas Valihrach | Milos Pekny | Elly M Hol
Glia | 2025

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.

Pubmed ID: 40735838

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: 'la Caixa' Foundation,
    Id: LCF/PR/HR21/52410002
  • Agency: European Joint Programme on Rare Diseases,
    Id: EJP RD 2019 ALEXANDER
  • Agency: Svenska Sällskapet för Medicinsk Forskning,
    Id: FO02021-0082
  • Agency: Svenska Sällskapet för Medicinsk Forskning,
    Id: FO2022-1032
  • Agency: Vetenskapsrådet,
    Id: 2018-02695
  • Agency: Vetenskapsrådet,
    Id: 2020-01148
  • Agency: Vetenskapsrådet,
    Id: 2019-00284
  • Agency: Söderberg's Foundations,
  • Agency: ALF Gothenburg,
    Id: 146051
  • Agency: ALF Gothenburg,
    Id: 965939
  • Agency: Petrus och Augusta Hedlunds Stiftelse,
    Id: M-2019-1026
  • Agency: Petrus och Augusta Hedlunds Stiftelse,
    Id: M2018-0803
  • Agency: Czech science foundation,
    Id: 24-11364S
  • Agency: Czech science foundation,
    Id: 24-12028S
  • Agency: Amlöv's Foundation,
  • Agency: Agencia Estatal de Investigación,
    Id: 10.13039/501100011033
  • Agency: Institute of Biotechnology of the Czech Academy of Sciences (IBT CAS) institutional support,
    Id: RVO 86652036
  • Agency: ZonMw, Netherlands
    Id: 463002004
  • Agency: MICIN and ERDF,
    Id: PID2021-126827OB-I00
  • Agency: MICIN and ERDF,
    Id: RTI2018-097624-B-I00
  • Agency: Comunidad Autónoma de Madrid,
    Id: PIPF-2022/SAL-GL-25771
  • Agency: ZonMw, Netherlands
    Id: 463002004

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