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Neural progenitor cells regulate microglia functions and activity

Nature Neuroscience volume 15, pages 1485–1487 (2012)Cite this article

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Abstract

We found mouse neural progenitor cells (NPCs) to have a secretory protein profile distinct from other brain cells and to modulate microglial activation, proliferation and phagocytosis. NPC-derived vascular endothelial growth factor was necessary and sufficient to exert at least some of these effects in mice. Thus, neural precursor cells may not only be shaped by microglia, but also regulate microglia functions and activity.

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Figure 1: Microglia and neural progenitor cells are well-positioned to interact in vivo.
Figure 2: NPCs secrete a distinct profile of signaling proteins and regulate microglial functions.
Figure 3: NPC-secreted VEGF is necessary and sufficient for the regulation of microglia.

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Acknowledgements

The authors wish to thank S. Villeda and R. Wabl for assistance with the neural progenitor cell cultures and M. Lochrie and the Stanford Neuroscience Gene Vector and Virus Core for generating the shRNA lentiviruses (supported by National Institute of Neurological Disorders and Stroke P30 core grant, NS069375-01A1). This work was supported by grants from the Department of Veterans Affairs (T.W.-C.) and US National Institutes of Health Institute on Aging (R01 AG027505, T.W.-C.), a California Initiative for Regenerative Medicine Award (T.W.-C.), a National Science Foundation predoctoral fellowship (K.I.M.), a Ruth L. Kirschstein NRSA predoctoral fellowship (1 F31 AG040877-01A1, K.I.M.), the Swiss National Science Foundation (PBBEB-117034 and PASMP3-123221/1, R.H.A.), the Evelyn L. Neizer Fund (R.H.A.), the American Heart Association (AHA 083527N, R.G.), and the Bechtel Foundation (R.G.).

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Author notes

  1. Robert H Andres, Takeshi Fukuhara, Maiko Hasegawa-Moriyama & Raphael Guzman

    Present address: Present addresses: Department of Neurosurgery, University of Berne, Inselspital, Berne, Switzerland (R.H.A.), Laboratory of Oncology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan (T.F.), Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan (M.H.-M.), Departments of Neurosurgery and Biomedicine, University of Basel, Basel, Switzerland (R.G.).,

  2. Kira I Mosher, Robert H Andres and Takeshi Fukuhara: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA

    Kira I Mosher, Takeshi Fukuhara, Gregor Bieri, Maiko Hasegawa-Moriyama, Yingbo He & Tony Wyss-Coray

  2. Neuroscience IDP Program, Stanford University School of Medicine, Stanford, California, USA

    Kira I Mosher & Gregor Bieri

  3. Department of Neurosurgery, Stanford University Medical Center, Stanford, California, USA

    Robert H Andres & Raphael Guzman

  4. Center for Tissue Regeneration, Repair and Restoration, Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA

    Tony Wyss-Coray

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Contributions

K.I.M. performed in vitro and in vivo experiments and analyzed data from in vivo experiments. R.H.A. performed in vivo experiments and analyzed data. T.F. performed in vitro experiments. G.B. assisted with the VEGF shRNA experiment. M.H.-M. and Y.H. provided conceptual advice and input. K.I.M. and T.W.-C. wrote the manuscript. R.G. and T.W.-C. supervised the project.

Corresponding authors

Correspondence to Raphael Guzman or Tony Wyss-Coray.

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The authors declare no competing financial interests.

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Mosher, K., Andres, R., Fukuhara, T. et al. Neural progenitor cells regulate microglia functions and activity. Nat Neurosci 15, 1485–1487 (2012). https://doi.org/10.1038/nn.3233

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