Open AccessNeurotrophic factors promote cholinergic differentiation in human embryonic stem cell‐derived neurons
Author(s) -
Nilbratt Mats,
Porras Omar,
Marutle Amelia,
Hovatta Outi,
Nordberg Agneta
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00916.x
Subject(s) - cholinergic , choline acetyltransferase , biology , cholinergic neuron , neuroscience , acetylcholine , nerve growth factor , neurotrophic factors , neurotrophin , ciliary neurotrophic factor , microbiology and biotechnology , brain derived neurotrophic factor , muscarinic acetylcholine receptor , medicine , endocrinology , receptor , biochemistry
Cholinergic neurotransmission is essential for many important functions in the brain, including cognitive mechanisms. Here we demonstrate that human embryonic stem (hES) cells differentiate into a population of neuronal cells that express the cholinergic enzyme choline acetyltransferase and homeobox proteins specifying neuronal progenitors of ventral telencephalic lineage. These differentiated cells express transcripts for cholinergic α 3 , α 4 and α 7 nicotinic acetylcholine (ACh) receptor subunits and for M1, M2 and M3 muscarinic acetylcholine receptor (mAChR) subtypes. Stimulation with brain‐derived neurotrophic factor, neurotrophin‐3, ciliary neurotrophic factor and nerve growth factor increases the proportion of cholinergic neurons. These cholinergic receptors also mediate ACh‐evoked increase in cytosolic calcium levels, and this response was unaffected by extracellular calcium removal and was abolished by the mAChR antagonist scopolamine. Our findings demonstrate expression of functional cholinergic receptors on hES cell‐derived neurons, which may provide a source of expandable cells to facilitate screening of novel cholinergic drugs and useful for evaluating cell transplantation in animal models of cholinergic dysfunction.