Detailed Information on Publication Record
2009
Wnt/beta-Catenin Signaling Blockade Promotes Neuronal Induction and Dopaminergic Differentiation in Embryonic Stem Cells
ČAJÁNEK, Lukáš, Diogo RIBEIRO, Isabel LISTE, Clare PARISH, Vítězslav BRYJA et. al.Basic information
Original name
Wnt/beta-Catenin Signaling Blockade Promotes Neuronal Induction and Dopaminergic Differentiation in Embryonic Stem Cells
Name in Czech
Zablokování signalizace přes Wnt/beta-katenin podporuje neurální indukci a dopaminergní diferenciaci v embryonálních kmenových buňkách
Authors
ČAJÁNEK, Lukáš (203 Czech Republic, guarantor), Diogo RIBEIRO (620 Portugal), Isabel LISTE (724 Spain), Clare PARISH (36 Australia), Vítězslav BRYJA (203 Czech Republic, belonging to the institution) and Ernest ARENAS (724 Spain)
Edition
Stem Cells, 2009, 1549-4918
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
Genetics and molecular biology
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
Impact factor
Impact factor: 7.747
RIV identification code
RIV/00216224:14310/09:00028624
Organization unit
Faculty of Science
UT WoS
000273569800005
Keywords in English
embryonic stem cells ; Wnt pathway ; dopaminergic neurons ; Wnt/ -catenin signaling
Změněno: 26/3/2012 14:17, prof. Mgr. Vítězslav Bryja, Ph.D.
V originále
Embryonic stem cells (ESCs) represent not only a promising source of cells for cell replacement therapy, but also a tool to study the molecular mechanisms underlying cellular signaling and dopaminergic (DA) neuron development. One of the main regulators of DA neuron development is Wnt signaling. Here we used mouse ESCs (mESCs) lacking Wnt1 or the low-density-lipoprotein receptor-related protein 6 (LRP6) to decipher the action of Wnt/ -catenin signaling on DA neuron development in mESCs. We provide evidence that the absence of LRP6 abrogates responsiveness of mESCs to Wnt ligand stimulation. Using two differentiation protocols we show that the loss of Wnt1 or LRP6 increases neuroectodermal differentiation and the number of mESC-derived DA neurons. These effects were similar to those observed following treatment of mESCs with the Wnt/ -catenin pathway inhibitor, Dickkopf1 (Dkk1). Combined, our results show that decreases in Wnt/ -catenin signaling enhance neuronal and DA differentiation of mESCs. These findings suggest: i) that Wnt1 or LRP6 are not strictly required for the DA differentiation of mESCs in vitro, ii) that the levels of morphogens and their activity in ESC cultures need to be optimized in order to improve DA differentiation, and iii) that by enhancing the differentiation and number of ESC-derived DA neurons with Dkk1, the application of ESCs for cell replacement therapy in Parkinson's disease may be improved.
In Czech
Embryonální kmenové buňky (ESCs) jsou vhodným nástrojem pro buněčnou terapii. V této studii jsme použili linie ES buněk, které byly geneticky upraveny tak aby neexrpimovali Wnt1, ligand Wnt dráhy, a Lrp6, klíčový koreceptor Wnt dráhy. S využitím těchto modelů ukazujeme, že pokles ve Wnt/beta-kateninové dráze zvyšuje neurální indukci z ES buněk a napomáhá diferenciaci do dopaminergních neuronů. Tento nález může být přímo napomoci aplikaci ES buněk v buněčné terapii Parkinsonovy choroby.
Links
| GA204/09/0498, research and development project |
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| MSM0021622430, plan (intention) |
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| 1658, interní kód MU |
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