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

Tamar Licht; Esther Sasson; Batia Bell; Myriam Grunewald; Saran Kumar; Tirzah Kreisel; Ayal Ben-Zvi; Eli Keshet

doi:10.7554/eLife.52134

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

Tamar Licht^*, Esther Sasson, Batia Bell, Myriam Grunewald, Saran Kumar, Tirzah Kreisel, Ayal Ben-Zvi, Eli Keshet^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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
Article number	e52134
Pages (from-to)	1-20
Number of pages	20
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.52134
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.

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10.7554/eLife.52134

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title = "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 >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 {\textquoteright}sensed{\textquoteright} by NSCs.",

author = "Tamar Licht and Esther Sasson and Batia Bell and Myriam Grunewald and Saran Kumar and Tirzah Kreisel and Ayal Ben-Zvi and Eli Keshet",

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: {\textcopyright} Licht et al.",

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AU - Kumar, Saran

AU - Kreisel, Tirzah

AU - Ben-Zvi, Ayal

AU - Keshet, Eli

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PY - 2020/6

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N2 - 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.

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JF - eLife

M1 - e52134

ER -

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

Abstract

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