Hippocampal neural stem cells facilitate access from circulation via apical cytoplasmic processes

Abstract

Blood vessels (BVs) are considered an integral component of neural stem cells (NSCs) niches. NSCs in the dentate gyrus (DG) have enigmatic elaborated apical cellular processes that are associated with BVs. Whether this contact serves as a mechanism for delivering circulating molecules is not known. Here we uncovered a previously unrecognized communication route allowing exclusive direct access of blood-borne substances to hippocampal NSCs. BBB-impermeable fluorescent tracer injected transcardially to mice is selectively uptaken by DG NSCs within a minute, via the vessel-associated apical processes. These processes, measured >30nm in diameter, establish direct membrane-to-membrane contact with endothelial cells in specialized areas of irregular endothelial basement membrane and enriched with vesicular activity. Doxorubicin, a brain-impermeable chemotherapeutic agent, is also readily and selectively uptaken by NSCs and reduces their proliferation, which might explain its problematic anti-neurogenic or cognitive side-effect. The newly-discovered NSC-BV communication route explains how circulatory neurogenic mediators are 'sensed' by NSCs.

Data availability

All data generated or analysed during this study are included in the manuscript.

Article and author information

Author details

  1. Tamar Licht

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    For correspondence
    tamarli@ekmd.huji.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2333-1665
  2. Esther Sasson

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Batia Bell

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Myriam Grunewald

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Saran Kumar

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Tirzah Kreisel

    Edmond and Lily Safra Center for Brain Sciences (ELSC), Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Ayal Ben-Zvi

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  8. Eli Keshet

    Developmental Biology and Cancer Research, Hebrew University, Jerusalem, Israel
    For correspondence
    elik@ekmd.huji.ac.il
    Competing interests
    The authors declare that no competing interests exist.

Funding

H2020 European Research Council (322692)

  • Tamar Licht
  • Myriam Grunewald
  • Saran Kumar
  • Eli Keshet

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal procedures were approved by the animal care and use committee of the Hebrew University (Protocol MD-14-13900-3). Every effort was made to minimize the numbers of animals and suffering.

Reviewing Editor

  1. Kate M Wassum, University of California, Los Angeles, United States

Publication history

  1. Received: September 23, 2019
  2. Accepted: June 3, 2020
  3. Accepted Manuscript published: June 4, 2020 (version 1)
  4. Version of Record published: June 16, 2020 (version 2)

Copyright

© 2020, Licht et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Tamar Licht
  2. Esther Sasson
  3. Batia Bell
  4. Myriam Grunewald
  5. Saran Kumar
  6. Tirzah Kreisel
  7. Ayal Ben-Zvi
  8. Eli Keshet
(2020)
Hippocampal neural stem cells facilitate access from circulation via apical cytoplasmic processes
eLife 9:e52134.
https://doi.org/10.7554/eLife.52134
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