发育中的人类中脑内的多巴胺能神经元前体表现出放射状胶质细胞的特征。

Dopamine neuron precursors within the developing human mesencephalon show radial glial characteristics.

作者信息

Hebsgaard Josephine B, Nelander Jenny, Sabelström Hanna, Jönsson Marie E, Stott Simon, Parmar Malin

机构信息

Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.

出版信息

Glia. 2009 Nov 15;57(15):1648-58. doi: 10.1002/glia.20877.

Abstract

Specification and differentiation of neural precursors into dopaminergic neurons within the ventral mesencephalon has been subject to much attention due to the implication of dopaminergic neurons in Parkinson's disease and the perspective of generating sources of therapeutically active cells to be used for cell replacement therapy for the disease. However, despite intensive research efforts, little is known about the characteristics of the dopamine neuron progenitors in human. We show that the dopamine neuron determinant LMX1a is expressed in the diencephalic and mesencephalic dopaminergic neuron domains during human development. Within the mesencephalon, LMX1a is expressed in the dopaminergic neurons and their progenitors located in the ventricular zone of the floor plate region. Furthermore, the neural progenitors in the developing human ventral mesencephalon have a radial morphology and express the radial glial markers Vimentin and BLBP. These radial glia are mitotic and act as precursors for the dopaminergic neurons. Finally, we show that progenitors isolated from the human ventral mesencephalon maintain their radial glial characteristics and neurogenic capacity after expansion in vitro, making them a promising future source of cells to be used in cell replacement therapy for Parkinson's disease.

摘要

由于多巴胺能神经元与帕金森病相关,且有望为该疾病生成用于细胞替代疗法的治疗活性细胞来源,因此腹侧中脑内神经前体向多巴胺能神经元的特化和分化备受关注。然而,尽管进行了大量深入研究,但对于人类多巴胺神经元祖细胞的特征仍知之甚少。我们发现,多巴胺神经元决定因子LMX1a在人类发育过程中,于间脑和中脑多巴胺能神经元区域表达。在中脑内,LMX1a在位于底板区域室管膜区的多巴胺能神经元及其祖细胞中表达。此外,发育中的人类腹侧中脑内的神经前体具有放射状形态,并表达放射状胶质细胞标志物波形蛋白和脑脂质结合蛋白。这些放射状胶质细胞具有有丝分裂能力,可作为多巴胺能神经元的前体。最后,我们表明,从人类腹侧中脑分离出的祖细胞在体外扩增后仍保持其放射状胶质细胞特征和神经发生能力,使其成为未来用于帕金森病细胞替代疗法的有前景的细胞来源。

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