Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair.
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.
Pubmed ID: 32894219 RIS Download
Research resources used in this publication
Additional research tools detected in this publication
- PRISM (RRID:SCR_005375)
- PeproTech (RRID:SCR_006802)
- Imaris (RRID:SCR_007370)
- Millipore (RRID:SCR_008983)
- Miltenyi Biotec (RRID:SCR_008984)
- Sigma-Aldrich (RRID:SCR_008988)
- FISHER (RRID:SCR_009181)
- Abcam (RRID:SCR_012931)
- BD Biosciences (RRID:SCR_013311)
- pheatmap (RRID:SCR_016418)
- HEK293 (RRID:CVCL_0045)
Antibodies used in this publication
- Phospho-Akt Pathway Antibody Sampler Kit (RRID:AB_10693765)
- Neuronal Class III beta-Tubulin (TUJ1) Monoclonal Antibody, Purified (RRID:AB_2313773)
- GPR62 Polyclonal Antibody (RRID:AB_2551116)
- ADCY5 antibody (RRID:AB_1140781)
- Mouse Monoclonal Antibody Specific for Human GFAP (RRID:AB_2833249)
- Anti-Olig2 antibody (RRID:AB_2810961)
- STEM121® (RRID:AB_2801314)
- C1q antibody [JL-1] (RRID:AB_10711046)
- Anti-Fibronectin antibody produced in rabbit (RRID:AB_476976)
- Glial Fibrillary Acidic Protein (Multipurpose) (RRID:AB_10013382)
- CD44-PE, human (RRID:AB_2658165)
- CD44 antibody [EPR1013Y] (RRID:AB_868936)
- CD133/1 Antibody, anti-human, Vio® Bright FITC (RRID:AB_2726215)
- Met (c-Met) antibody [EP1454Y] (RRID:AB_880695)
Associated grants
- Agency: Craig H. Neilsen Foundation, International
Id: CHN-316291 - Agency: Christopher and Dana Reeve Foundation, International
Id: AAC-2013(5) - Agency: NIH HHS, United States
Id: 1S10OD016328-01
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This is a list of tools and resources that we have found mentioned in this publication.
PRISM (tool)
RRID:SCR_005375
THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsImaris (tool)
RRID:SCR_007370
Imaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
View all literature mentionsMiltenyi Biotec (tool)
RRID:SCR_008984
An Organization portal, Antibody supplier, Service resource,
View all literature mentionsSigma-Aldrich (tool)
RRID:SCR_008988
American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsFISHER (tool)
RRID:SCR_009181
THIS RESOURCE IS NO LONGER IN SERVICE, documented on February 1st, 2022. Software application for genetic analysis of classical biometric traits like blood pressure or height that are caused by a combination of polygenic inheritance and complex environmental forces. (entry from Genetic Analysis Software)
View all literature mentionsAbcam (tool)
RRID:SCR_012931
A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionspheatmap (tool)
RRID:SCR_016418
Software tool as a function in R to draw clustered heatmaps for better control over graphical parameters.
View all literature mentionsHEK293 (tool)
RRID:CVCL_0045
Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsPhospho-Akt Pathway Antibody Sampler Kit (antibody)
RRID:AB_10693765
This unknown targets Phospho-Akt Pathway Sampler Kit
View all literature mentionsNeuronal Class III beta-Tubulin (TUJ1) Monoclonal Antibody, Purified (antibody)
RRID:AB_2313773
This monoclonal targets Neuronal Class III beta-Tubulin (TUJ1) Purified
View all literature mentionsGPR62 Polyclonal Antibody (antibody)
RRID:AB_2551116
This unknown targets GPR62
View all literature mentionsADCY5 antibody (antibody)
RRID:AB_1140781
This polyclonal targets ADCY5 antibody
View all literature mentionsMouse Monoclonal Antibody Specific for Human GFAP (antibody)
RRID:AB_2833249
This monoclonal targets GFAP
View all literature mentionsAnti-Olig2 antibody (antibody)
RRID:AB_2810961
This polyclonal targets Olig2
View all literature mentionsSTEM121® (antibody)
RRID:AB_2801314
This monoclonal targets cytoplasmic protein
View all literature mentionsC1q antibody [JL-1] (antibody)
RRID:AB_10711046
This monoclonal targets C1q antibody [JL-1]
View all literature mentionsAnti-Fibronectin antibody produced in rabbit (antibody)
RRID:AB_476976
This unknown targets Fibronectin
View all literature mentionsGlial Fibrillary Acidic Protein (Multipurpose) (antibody)
RRID:AB_10013382
This polyclonal targets GFAP
View all literature mentionsCD44 antibody [EPR1013Y] (antibody)
RRID:AB_868936
This monoclonal targets Human CD44
View all literature mentionsCD133/1 Antibody, anti-human, Vio® Bright FITC (antibody)
RRID:AB_2726215
This monoclonal targets CD133/1
View all literature mentionsMet (c-Met) antibody [EP1454Y] (antibody)
RRID:AB_880695
This monoclonal targets Synthetic peptide corresponding to residues near the N-terminus of human Met (c-Met).
View all literature mentionsSnapGene (annotation tool)
RRID:SCR_015052
Molecular biology software for visualizing and documenting gene constructs for InFusion cloning, Gibson assembly, restriction cloning, PCR, and mutagenesis.
View all literature mentionsImageJ (software resource)
RRID:SCR_003070
Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsGraphPad Prism (software resource)
RRID:SCR_002798
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentions
