Regulation of human neural precursor cells by laminin and integrins.
Deciphering the factors that regulate human neural stem cells will greatly aid in their use as models of development and as therapeutic agents. The extracellular matrix (ECM) is a component of stem cell niches in vivo and regulates multiple functions in diverse cell types, yet little is known about its effects on human neural stem/precursor cells (NSPCs). We therefore plated human NSPCs on four different substrates (poly-L-ornithine, fibronectin, laminin, and matrigel) and compared their responses with those of mouse NSPCs. Compared with the other substrates, laminin matrices enhanced NSPC migration, expansion, differentiation into neurons and astrocytes, and elongation of neurites from NSPC-derived neurons. Laminin had a similar spectrum of effects on both human and mouse cells, highlighting the evolutionary conservation of NSPC regulation by this component of the ECM. Flow cytometry revealed that human NSPCs express on their cell surfaces the laminin-binding integrins alpha3, alpha6, alpha7, beta1, and beta4, and function-blocking antibodies to the alpha6 subunit confirmed a role for integrins in laminin-dependent migration of human NSPCs. These results define laminin and its integrin receptors as key regulators of human NSPCs.
Flanagan
Lisa A
LA
Pathology Department, School of Medicine, University of California Irvine, California 92697-4800, USA. emonuki@uci.edu
Rebaza
Liza M
LM
Derzic
Stanislava
S
Schwartz
Philip H
PH
Monuki
Edwin S
ES
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology*; D010455:Peptides / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
D004338:Drug Combinations; D016023:Integrins; D007797:Laminin; D010455:Peptides; D011509:Proteoglycans; C059485:matrigel; C008973:polyornithine; D003094:Collagen