中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (4): 692-693.doi: 10.4103/1673-5374.295316

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

模式的不一致性限制了来自人类诱导多能干细胞的多巴胺能神经元的真正潜能

  

  • 出版日期:2021-04-15 发布日期:2020-12-21
  • 基金资助:


Patterning inconsistencies restrict the true potential of dopaminergic neurons derived from human induced pluripotent stem cells 

Sameehan Mahajani*, Mathias Bähr, Sebastian Kügler   

  1. Department of Neurology, University Medical Center Göttingen, Göttingen, Germany 
    (Mahajani S, Bähr M, Kügler S)
    Center for Nanoscale Microscopy and Molecular Physiology of the Brain at Department of Neurology, University Medical Center Göttingen, Göttingen, Germany (Mahajani S, Bähr M, Kügler S)
    Current affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA (Mahajani S)
  • Online:2021-04-15 Published:2020-12-21
  • Contact: Sameehan Mahajani, PhD, mahajani@stanford.edu.
  • Supported by:


摘要: https://orcid.org/0000-0002-5705-2122 (Sameehan Mahajani) 

Abstract: Human induced pluripotent stem cells (hiPSCs) are multipotent stem cells genetically reprogrammed using transcription factors, such as Sox2, c-Myc, Oct3/4 and Klf4 (Takahashi and Yamanaka, 2006) from fibroblasts, derived from either patient or control individuals. These factors are highly expressed in embryonic stem cells, and their overexpression can induce pluripotency in human somatic cells such as fibroblasts. Upon the generation of hiPSCs after reprogramming, these cells can be further differentiated into multiple neuronal cell types by using a strictly designed protocol. This process is known as patterning. Correct use of these hiPSCs derived neurons holds immense potential for researchers to uncover the underpinnings of disease pathophysiology and therefore is considered as a powerful tool. For example, in the context of Parkinson’s disease (PD), numerous publications have highlighted the aggregation of an abnormally folded protein, α-Synuclein that forms intracellular inclusions in the cell body and neurite processes known as Lewy bodies. However, the mechanisms that cause neurodegeneration specifically in dopaminergic neurons as compared to other neuronal subtypes are still unknown. Unfortunately, it is rather difficult to culture genuine dopaminergic neurons from rodent embryos in sufficient amounts. Therefore, generating human dopaminergic or glutamatergic neurons from hiPSCs to determine the selective detrimental effect of α-Synuclein could offer an immensely valuable outlook. The use of hiPSCs derived dopaminergic neurons could enable us to decipher the pathophysiological mechanisms of this selective neurodegeneration in an in-vitro culture system. However, there are several inconsistences in the field of hiPSCs derived dopaminergic neurons, which need to be addressed in order to generate reliable, reproducible and efficient protocols for their patterning.