Differentiation of human ES and Parkinson's disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acid.
Differentiation of human ES and Parkinson's disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acid.
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DOI：
10.1016/j.mcn.2010.06.017
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发表时间：
2010-11
影响因子：
3.5
通讯作者：
Isacson, Ole
中科院分区：
文献类型：
--
作者：
Cooper, Oliver;Hargus, Gunnar;Deleidi, Michela;Blak, Alexandra;Osborn, Teresia;Marlow, Elizabeth;Lee, Kristen;Levy, Adam;Perez-Torres, Eduardo;Yow, Alyssa;Isacson, Ole
The cardinal motor symptoms of Parkinson’s disease (PD) are caused by the vulnerability to dysfunction and degeneration of ventral midbrain (VM) dopaminergic (DA) neurons. A major limitation for experimental studies of current ES/iPS cell differentiation protocols is the lack of VM DA neurons with a stable phenotype as defined by an expression marker code of FOXA2/TH/β-tubulin. Here we demonstrate a combination of three modifications that were required to produce VM DA neurons. Firstly, early and specific exposure to 10−8M (low dose) retinoic acid improved the regional identity of neural progenitor cells derived from human ES cells, PD or healthy subject-specific iPS cells. Secondly, a high activity form of human sonic hedgehog established a sizeable FOXA2+ neural progenitor cell population in vitro. Thirdly, early exposure to FGF8a, rather than Fgf8b, and WNT1 was required for robust differentiation of the FOXA2+ floor plate-like human neural progenitor cells into FOXA2+ DA neurons. FOXA2+ DA neurons were also generated when this protocol was adapted to feeder-free conditions. In summary, this new human ES and iPS cell differentiation protocol using FGF8a, WNT1, low dose retinoic acid and a high activity form of SHH can generate human VM DA neurons that are required for relevant new bioassays, drug discovery and cell based therapies for PD.
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DOI：
10.1634/stemcells.2008-0543
发表时间：
2009-01
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Erceg S;Ronaghi M;Stojković M
通讯作者：
Stojković M
影响因子：
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DOI：
10.1111/j.1749-6632.1992.tb24523.x
发表时间：
1992-05-11
影响因子：
5.2
作者：
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通讯作者：
BROOKS, BA
影响因子：
5.2
作者：
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通讯作者：
Iacovitti, Lorraine
影响因子：
5.2
作者：
Chiba, Shunmei;Lee, Young Mook;Freed, Curt R.
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Freed, Curt R.