Open AccessIncreasing Doublecortin Expression Promotes Migration of Human Embryonic Stem Cell‐Derived Neurons
Author(s) -
Filipovic Radmila,
Santhosh Kumar Saranya,
Fiondella Chris,
Loturco Joseph
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1162
Subject(s) - biology , embryonic stem cell , doublecortin , microbiology and biotechnology , stem cell , neurogenesis , neuroscience , genetics , gene , dentate gyrus , hippocampal formation
Human embryonic stem cell‐derived neuronal progenitors (hNPs) provide a potential source for cellular replacement following neurodegenerative diseases. One of the greatest challenges for future neuron replacement therapies will be to control extensive cell proliferation and stimulate cell migration of transplanted cells. The doublecortin (DCX) gene encodes the protein DCX, a microtubule‐associated protein essential for the migration of neurons in the human brain. In this study, we tested whether increasing the expression of DCX in hNPs would favorably alter their proliferation and migration. Migration and proliferation of hNPs was compared between hNPs expressing a bicistronic DCX/IRES‐GFP transgene and those expressing a green fluorescent protein (GFP) transgene introduced by piggyBac ‐mediated transposition. The DCX‐transfected hNPs showed a significant decrease in their proliferation and migrated significantly further on two different substrates, Matrigel and brain slices. Additionally, a dense network of nestin‐positive (+) and vimentin+ fibers were found to extend from neurospheres transplanted onto brain slices, and this fiber growth was increased from neurospheres containing DCX‐transfected hNPs. In summary, our results show that increased DCX expression inhibits proliferation and promotes migration of hNPs. S tem C ells 2012;30:1852–1862