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 >30 nm 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.
Original language | American English |
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Article number | e52134 |
Pages (from-to) | 1-20 |
Number of pages | 20 |
Journal | eLife |
Volume | 9 |
DOIs | |
State | Published - Jun 2020 |
Bibliographical note
Funding Information:We wish to thank Yuval Dor and Itzhak Dershowitz for helpful suggestions, and assistance, Yael Friedman and Eddie Berenshtein for TEM support. This work was supported by the European Research Council (ERC(grant, project VASNICHE (Grant # 322692) and the Israel Science Foundation (grants # 1882/16 and # 2402/16) to ABZ. H2020 European Research Council- 322692- Tamar Licht; Myriam Grunewald- Saran Kumar, Eli Keshet; Israel Science Foundation- 1882/16- Esther Sasson, Batia Bell, Ayal Ben-Zvi; Israel Science Foundation- 2402/16- Esther Sasson, Batia Bell, Ayal Ben-Zvi.
Funding Information:
We wish to thank Yuval Dor and Itzhak Dershowitz for helpful suggestions,and assistance, Yael Friedman and Eddie Berenshtein for TEM support. This work was supported by the European Research Council (ERC(grant, project VASNICHE (Grant # 322692) and the Israel Science Foundation (grants # 1882/16 and # 2402/16) to ABZ.
Publisher Copyright:
© Licht et al.