RESUMO
Optic atrophy 1 (OPA1), a GTPase at the inner mitochondrial membrane involved in regulating mitochondrial fusion, stability, and energy output, is known to be crucial for neural development: Opa1 heterozygous mice show abnormal brain development, and inactivating mutations in OPA1 are linked to human neurological disorders. Here, we used genetically modified human embryonic and patient-derived induced pluripotent stem cells and reveal that OPA1 haploinsufficiency leads to aberrant nuclear DNA methylation and significantly alters the transcriptional circuitry in neural progenitor cells (NPCs). For instance, expression of the forkhead box G1 transcription factor, which is needed for GABAergic neuronal development, is repressed in OPA1+/- NPCs. Supporting this finding, OPA1+/- NPCs cannot give rise to GABAergic interneurons, whereas formation of glutamatergic neurons is not affected. Taken together, our data reveal that OPA1 controls nuclear DNA methylation and expression of key transcription factors needed for proper neural cell specification.
RESUMO
The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has raised extreme hope among both scientists and society by means of development of personalized and regenerative medicine. The field of stem cell research has been accelerating with a drastic speed afterwards and many iPSC lines has been produced for understanding the mechanisms of many debilitating diseases which arise in a variety of organ systems. In this review article we try to focus on the current research regarding the use of iPSCs in both disease modeling and regeneration.
