In Vitro Modelling of Cortical Neurogenesis by Sequential Induction of Human Umbilical Cord Blood Stem Cells

被引:11
作者
Ali, Hamad [1 ,2 ]
Forraz, Nicolas [1 ,3 ]
McGuckin, Colin P. [1 ,3 ]
Jurga, Marcin [1 ,3 ]
Lindsay, Susan [1 ]
Ip, Bui Kar [1 ,4 ]
Trevelyan, Andrew [4 ]
Basford, Christina [1 ]
Habibollah, Saba [1 ]
Ahmad, Sajjad [1 ]
Clowry, Gavin J. [4 ]
Bayatti, Nadhim [1 ,4 ]
机构
[1] Newcastle Univ, Inst Med Genet, Int Ctr Life, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England
[2] Kuwait Univ, Dept Pathol, Fac Med, Safat, State Of Kuwait, Kuwait
[3] CTI LYON, Cell Therapy Res Inst, F-69800 St Priest, France
[4] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
基金
英国惠康基金;
关键词
Neocortex; Glutamic acid; Cord blood; Stem cells; Neurons; HUMAN CEREBRAL-CORTEX; EMBRYONIC-LIKE CELLS; RADIAL GLIA; STEM/PROGENITOR CELLS; SUBVENTRICULAR ZONE; HUMAN NEOCORTEX; NMDA RECEPTORS; MESSENGER-RNA; NEURONS; DIFFERENTIATION;
D O I
10.1007/s12015-011-9287-x
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Neurogenesis of excitatory neurons in the developing human cerebral neocortex is a complex and dynamic set of processes and the exact mechanisms controlling the specification of human neocortical neuron subtypes are poorly understood due to lack of relevant cell models available. It has been shown that the transcription factors Pax6, Tbr2 and Tbr1, which are sequentially expressed in the rodent neocortex, regulate and define corticogenesis of glutamatergic neocortical neurons. In humans the homologues of these genes are generally expressed in a similar pattern, but with some differences. In this study, we used purified human umbilical cord blood stem cells, expressing pluripotency marker genes (OCT4, SOX2 and NANOG), to model human neocortical neurogenesis in vitro. We analyzed the expression patterns of PAX6, TBR2 and TBR1, at both protein and mRNA levels, throughout the 24 days of a sequential neuronal induction protocol. Their expression patterns correlated with those found in the developing human neocortex where they define different developmental stages of neocortical neurons. The derived cord blood neuron-like cells expressed a number of neuronal markers. They also expressed components of glutamatergic neurotransmission including glutamate receptor subunits and transporters, and generated calcium influxes upon stimulation with glutamate. Thus we have demonstrated that it is possible to model neocortical neurogenesis using cord blood stem cells in vitro. This may allow detailed analysis of the molecular mechanisms regulating neocortical neuronal specification, thus aiding the development of potential therapeutic tools for diseases and injuries of the cerebral cortex.
引用
收藏
页码:210 / 223
页数:14
相关论文
共 66 条
[61]   Voltage-sensitive and ligand-gated channels in differentiating neural stem-like cells derived from the nonhematopoietic fraction of human umbilical cord blood [J].
Sun, W ;
Buzanska, L ;
Domanska-Lanik, K ;
Salvi, RJ ;
Stachowiak, MK .
STEM CELLS, 2005, 23 (07) :931-945
[62]   Embryonic stem cell lines derived from human blastocysts [J].
Thomson, JA ;
Itskovitz-Eldor, J ;
Shapiro, SS ;
Waknitz, MA ;
Swiergiel, JJ ;
Marshall, VS ;
Jones, JM .
SCIENCE, 1998, 282 (5391) :1145-1147
[63]   Mitochondrial DNA mutations affect calcium handling in differentiated neurons [J].
Trevelyan, Andrew J. ;
Kirby, Denise M. ;
Smulders-Srinivasan, Tora K. ;
Nooteboom, Marco ;
Acin-Perez, Rebeca ;
Antonio Enriquez, Jose ;
Whittington, Miles A. ;
Lightowlers, Robert N. ;
Turnbull, Doug M. .
BRAIN, 2010, 133 :787-796
[64]   A PCR primer bank for quantitative gene expression analysis [J].
Wang, XW ;
Seed, B .
NUCLEIC ACIDS RESEARCH, 2003, 31 (24)
[65]   Cord Blood-Derived Neurons Are Originated from CD133+/CD34 Stem/Progenitor Cells in a Cell-to-Cell Contact Dependent Manner [J].
Zangiacomi, Vincent ;
Balon, Norbert ;
Maddens, Stephane ;
Lapierre, Valerie ;
Tiberghien, Pierre ;
Schlichter, Remy ;
Versaux-Botteri, Claudine ;
Deschaseaux, Frederic .
STEM CELLS AND DEVELOPMENT, 2008, 17 (05) :1005-1016
[66]   Human Cord Blood-Derived Hematopoietic and Neural-Like Stem/Progenitor Cells Are Attracted by the Neurotransmitter GABA [J].
Zangiacomi, Vincent ;
Balon, Norbert ;
Maddens, Stephane ;
Tiberghien, Pierre ;
Versaux-Botteri, Claudine ;
Deschaseaux, Frederic .
STEM CELLS AND DEVELOPMENT, 2009, 18 (09) :1369-1377