Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair

eLife, 2020 · DOI: https://doi.org/10.7554/eLife.55732 · Published: September 7, 2020

Immunology Neurology Regenerative Medicine & Stem Cells

Simple Explanation

This research explores how the immune protein C1q affects neural stem cells (NSCs), which are important for brain repair. It identifies five proteins on NSCs that interact with C1q, suggesting C1q can directly signal to these cells. One of these proteins, CD44, is shown to mediate C1q's effects on NSC movement and signaling. Blocking CD44 reduces NSC migration to injury sites and improves recovery after spinal cord injury in mice. The study suggests modifying C1q-receptor interactions could improve stem cell therapies for brain and spinal cord injuries, offering a way to enhance the benefits of these treatments.

Study Duration

Not specified

Participants

hNSC and mNSC cell lines, Rag1 and NODSCID mice

Evidence Level

Level 1, In vitro and in vivo study

Key Findings

1
C1q activates specific intracellular signaling pathways in NSC to modulate NSC behavior.
2
CD44 mediates C1q induced p-ERK intracellular signaling activation and migration in NSC in vitro.
3
CD44 KO decreases hNSC localization at the SCI epicenter, modulating astroglial fate and rescuing the capacity of hNSC to promote locomotor recovery after transplantation into the acute SCI microenvironment.

Research Summary

This study demonstrates evidence for a receptor-mediated signaling role for complement C1q in the CNS, modulating NSC migration, proliferation, and lineage commitment. The study defines and validates five cell surface signaling/receptor candidate proteins, all of which represent novel C1q binding partners. In vivo genetic deletion of CD44 in hNSC restored the capacity of hNSC to drive locomotor recovery after acute SCI transplantation, expanding the therapeutic window to the acute injury microenvironment.

Practical Implications

Therapeutic Potential

Modifying C1q-receptor interactions can enhance stem cell therapies for CNS injuries.

Targeted Therapies

Targeting specific receptors on transplanted cells, rather than broad inflammatory agents, may improve outcomes.

Understanding Neuroinflammation

The study broadens the understanding of how inflammatory proteins affect NSC behavior in various CNS conditions.

Study Limitations

1
The study cannot rule out the potential contribution of other CD44 ligands in the SCI microenvironment.
2
Further studies are needed to determine the biological functionalities of the other novel ligand-receptor interactions.
3
The use of immunodeficient mice may not fully represent the immune response in humans.

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