The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation

被引：23
|
作者：
Gyllborg, Daniel [1 ]
Ahmed, Maqsood [2 ]
Toledo, Enrique M. [1 ,3 ]
Theofilopoulos, Spyridon [1 ,4 ]
Yang, Shanzheng [1 ]
Ffrench-Constant, Charles [2 ]
Arenas, Ernest [1 ]
机构：
[1] Karolinska Inst, Dept Med Biochem & Biophys, Lab Mol Neurobiol, S-17177 Stockholm, Sweden
[2] Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland
[3] Novo Nordisk Res Ctr Oxford, Cellular Syst Genom, Oxford OX3 7BN, England
[4] Swansea Univ, Med Sch, Inst Life Sci 1, Swansea SA2 8PP, W Glam, Wales
来源：
STEM CELL REPORTS | 2018年 / 11卷 / 03期
基金：
英国惠康基金; 英国生物技术与生命科学研究理事会; 瑞典研究理事会;
关键词：
F-SPONDIN; IN-VIVO; NEURON DEVELOPMENT; WNT/BETA-CATENIN; SUBSTANTIA-NIGRA; STEM-CELLS; LGR5; RECEPTORS; PROGENITORS; IDENTIFICATION;
D O I：
10.1016/j.stemcr.2018.07.014
中图分类号：
Q813 [细胞工程];
学科分类号：
摘要：
The development of midbrain dopaminergic (mDA) neurons is controlled by multiple morphogens and transcription factors. However, little is known about the role of extracellular matrix proteins in this process. Here we examined the function of roof plate-specific spondins (RSPO1-4) and the floor plate-specific, spondin 1 (SPON1). Only RSPO2 and SPON1 were expressed at high levels duringmDA neurogenesis, and the receptor LGR5 was expressed by midbrain floor plate progenitors. Surprisingly, RSPO2, but not SPON1, specifically promoted the differentiation of mDA neuroblasts into mDA neurons in mouse primary cultures and embryonic stem cells (ESCs). In addition, RSPO2 was found to promote not only mDA differentiation, but also mDA neurogenesis in human ESCs. Our results thus uncover an unexpected function of the matricellular protein RSPO2 and suggest an application to improve mDA neurogenesis and differentiation in human stem cell preparations destined to cell replacement therapy or drug discovery for Parkinson disease.
引用
收藏
页码：651 / 664
页数：14
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