Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair
Journal
eLife
ISSN
2050-084X
Date Issued
2020
Author(s)
Katja M Piltti
Mitra J Hooshmand
Aileen A Nava
Anita Lakatos
Brianna G Feld
Dana Creasman
Paul D Gershon
Aileen Anderson
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>C1q plays a key role as a recognition molecule in the immune system, driving autocatalytic complement cascade activation and acting as an opsonin. We have previously reported a non-immune role of complement C1q modulating the migration and fate of human neural stem cells (hNSC); however, the mechanism underlying these effects has not yet been identified. Here, we show for the first time that C1q acts as a functional hNSC ligand, inducing intracellular signaling to control cell behavior. Using an unbiased screening strategy, we identified five transmembrane C1q signaling/receptor candidates in hNSC (CD44, GPR62, BAI1, c-MET, and ADCY5). We further investigated the interaction between C1q and CD44 , demonstrating that CD44 mediates C1q induced hNSC signaling and chemotaxis in vitro, and hNSC migration and functional repair in vivo after spinal cord injury. These results reveal a receptor-mediated mechanism for C1q modulation of NSC behavior and show that modification of C1q receptor expression can expand the therapeutic window for hNSC transplantation.</jats:p>
Cite this document
Benavente, F., Piltti, K. M., Hooshmand, M. J., Nava, A. A., Lakatos, A., Feld, B. G., Creasman, D., Gershon, P. D., & Anderson, A. (2020). Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair. eLife, 9, e55732. https://doi.org/10.7554/eLife.55732
Subjects
animals
;
cell differentiation
;
cell transplantation
;
cells, cultured
;
complement c1q
;
hyaluronan receptors
;
membrane glycoproteins
;
mice
;
neural stem cells
;
receptors, complement
;
signal transduction
;
spinal cord injuries
;
brain derived neurotrophic factor
;
complement component c1q
;
g protein coupled receptor
;
glial cell line derived neurotrophic factor
;
glial fibrillary acidic protein
;
hyaluronic acid
;
immunoglobulin g
;
low density lipoprotein receptor related protein 6
;
neutralizing antibody
;
opsonin
;
osteopontin
;
scatter factor
;
transcription factor sox2
;
complement 1q receptor
;
complement component c1q
;
complement receptor
;
hyaluronic acid binding protein
;
membrane protein
;
adaptive immunity
;
angiogenesis
;
animal cell
;
animal experiment
;
animal model
;
antibody labeling
;
article
;
astrocyte
;
biotinylation
;
carcinogenesis
;
cell differentiation
;
cell function
;
cell migration
;
cell proliferation
;
cell viability
;
chemotaxis
;
chemotaxis assay
;
confocal microscopy
;
controlled study
;
dendrite
;
experimental behavioral test
;
extracellular matrix
;
female
;
flow cytometry
;
fluorescence activated cell sorting
;
gene deletion
;
gene editing
;
gene expression
;
genotype
;
histology
;
human
;
human cell
;
immune system
;
immunoblotting
;
immunocytochemistry
;
immunofluorescence
;
immunohistochemistry
;
immunohistology
;
in situ hybridization
;
induced pluripotent stem cell
;
innate immunity
;
intracellular signaling
;
laminectomy
;
locomotion
;
macrophage
;
mass spectrometry
;
mesenchymal stem cell
;
microarray analysis
;
mouse
;
nerve degeneration
;
neural stem cell
;
neurite outgrowth
;
nonhuman
;
oncogene
;
open field test
;
phenotype
;
protein expression
;
protein phosphorylation
;
rna extraction
;
rna sequence
;
sanger sequencing
;
signal transduction
;
spinal cord injury
;
stem cell
;
umbilical cord blood
;
western blotting
;
whole cell patch clamp
;
zebra fish
;
animal
;
cell culture
;
cell transplantation
;
metabolism
;
neural stem cell
;
signal transduction