TY - JOUR
KW - POLG
KW - cortical organoids
KW - iPSC
KW - mitochondrial function
KW - neuron
AU - Anbin Chen
AU - Tsering Yangzom
AU - Yu Hong
AU - Bjørn Christian Lundberg
AU - Gareth John Sullivan
AU - Charalampos Tzoulis
AU - Laurence A. Bindoff
AU - Kristina Xiao Liang
AB - In this research, a 3D brain organoid model is developed to study POLG-related encephalopathy, a mitochondrial disease stemming from POLG mutations. Induced pluripotent stem cells (iPSCs) derived from patients with these mutations is utilized to generate cortical organoids, which exhibited typical features of the diseases with POLG mutations, such as altered morphology, neuronal loss, and mitochondiral DNA (mtDNA) depletion. Significant dysregulation is also identified in pathways crucial for neuronal development and function, alongside upregulated NOTCH and JAK-STAT signaling pathways. Metformin treatment ameliorated many of these abnormalities, except for the persistent affliction of inhibitory dopamine-glutamate (DA GLU) neurons. This novel model effectively mirrors both the molecular and pathological attributes of diseases with POLG mutations, providing a valuable tool for mechanistic understanding and therapeutic screening for POLG-related disorders and other conditions characterized by compromised neuronal mtDNA maintenance and complex I deficiency.
BT - Advanced Science
DA - 2024
DO - 10.1002/advs.202307136
IS - 18
LA - en
N2 - In this research, a 3D brain organoid model is developed to study POLG-related encephalopathy, a mitochondrial disease stemming from POLG mutations. Induced pluripotent stem cells (iPSCs) derived from patients with these mutations is utilized to generate cortical organoids, which exhibited typical features of the diseases with POLG mutations, such as altered morphology, neuronal loss, and mitochondiral DNA (mtDNA) depletion. Significant dysregulation is also identified in pathways crucial for neuronal development and function, alongside upregulated NOTCH and JAK-STAT signaling pathways. Metformin treatment ameliorated many of these abnormalities, except for the persistent affliction of inhibitory dopamine-glutamate (DA GLU) neurons. This novel model effectively mirrors both the molecular and pathological attributes of diseases with POLG mutations, providing a valuable tool for mechanistic understanding and therapeutic screening for POLG-related disorders and other conditions characterized by compromised neuronal mtDNA maintenance and complex I deficiency.
PY - 2024
EP - 2307136
T2 - Advanced Science
TI - Hallmark Molecular and Pathological Features of POLG Disease are Recapitulated in Cerebral Organoids
UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202307136
VL - 11
Y2 - 2025-01-13
SN - 2198-3844
ER -