Journal of Inherited Metabolic Disease

, Volume 41, Issue 6, pp 1103–1116 | Cite as

Induced pluripotent stem cells (iPSCs) as model to study inherited defects of neurotransmission in inborn errors of metabolism

  • Sabine Jung-KlawitterEmail author
  • Thomas Opladen


The ability to reprogram somatic cells to induced pluripotent stem cells (iPSCs) has revolutionized the way of modeling human disease. Especially for the modeling of rare human monogenetic diseases with limited numbers of patients available worldwide and limited access to the mostly affected tissues, iPSCs have become an invaluable tool. To study rare diseases affecting neurotransmitter biosynthesis and neurotransmission, stem cell models carrying patient-specific mutations have become highly important as most of the cell types present in the human brain and the central nervous system (CNS), including motoneurons, neurons, oligodendrocytes, astrocytes, and microglia, can be differentiated from iPSCs following distinct developmental programs. Differentiation can be performed using classical 2D differentiation protocols, thereby generating specific subtypes of neurons or glial cells in a dish. On the other side, 3D differentiation into “organoids” opened new ways to study misregulated developmental processes associated with rare neurological and neurometabolic diseases. For the analysis of defects in neurotransmission associated with rare neurometabolic diseases, different types of brain organoids have been made available during the last years including forebrain, midbrain and cerebral organoids. In this review, we illustrate reprogramming of somatic cells to iPSCs, differentiation in 2D and 3D, as well as already available disease-specific iPSC models, and discuss current and future applications of these techniques.



We acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) and Ruprecht-Karls-University Heidelberg within the funding programme Open Access Publishing. This study was supported in parts by the Dietmar Hopp Stiftung, St. Leon-Rot, Germany.


This study was supported by the Dietmar Hopp Foundation St. Leon-Rot (Grant No. 23011205 to TO).

Compliance with ethical standards

Conflict of interest

S. Jung-Klawitter and T. Opladen declare that they have no conflict of interest.

Supplementary material

10545_2018_225_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 21 kb)


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© SSIEM 2018

Authors and Affiliations

  1. 1.Department of General Pediatrics, Division of Neuropediatrics and Metabolic MedicineUniversity Hospital HeidelbergHeidelbergGermany

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