Evidence map›Paper›PMID 40447618›Full record

ArticleNature communications2025

Human endothelial cells promote a human neural stem cell type B phenotype via Notch signaling.

Brenda Gutierrez, Tzu Chia Liu, Carly Rodriguez, Oier Pastor-Alonso, Hannah Lambing, Mercedes F Paredes, Lisa A Flanagan

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Routes of precursors' migration in remyelination.Brain : a journal of neurology · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Brenda GutierrezDepartment of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA. bgutier4@uci.edu.
Tzu Chia LiuDepartment of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-1286-6333
Carly RodriguezSue & Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.
Oier Pastor-AlonsoNeurology Department and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8075-1768
Hannah LambingNeurology Department and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA, USA.
Mercedes F ParedesNeurology Department and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-2503-1447
Lisa A FlanaganDepartment of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA. lisa.flanagan@uci.edu.ORCID http://orcid.org/0000-0002-1120-8902

Funding

Regulation of Cellular Pathwaysin Human Brain DevelopmentP01NS083513 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ALVAREZ-BUYLLA, ARTURO · 2014 to 2024
$12.6M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008620 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI GOLDIN, ALAN L · 1999 to 2023
$8.1M
Training Program in Stem Cell Translational Medicine for Neurological DisordersT32NS082174 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PETER John DONOVAN, Leslie Michels Thompson · 2013 to 2026
$3.3M
Gyrencephalic Model for Neurodevelopmental Disease and Postnatal Cortical Therapeutic InterventionsDP2NS122550 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PAREDES, MERCEDES · 2020 to 2020
$2.4M
Human neural stem cell and endothelial cell reciprocal interactions govern cell functionR01NS119829 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI FLANAGAN, LISA A · 2021 to 2025
$2.0M
A Vascularized Micro-Organ platform for the study of Brain-BBB-Blood interactionR33HL154307 · NHLBI · UNIVERSITY OF CALIFORNIA-IRVINE · PI HUGHES, CHRISTOPHER C. W., THOMPSON, LESLIE MICHELS · 2022 to 2024
$1.9M
A Vascularized Micro-Organ platform for the study of Brain-BBB-Blood interactionR61HL154307 · NHLBI · UNIVERSITY OF CALIFORNIA-IRVINE · PI HUGHES, CHRISTOPHER C. W., THOMPSON, LESLIE MICHELS · 2020 to 2021
$1.3M
Reciprocal communication between human neural stem cells and human endothelial cellsF31NS118845 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI GUTIERREZ, BRENDA · 2020 to 2023
$109k
National Science Foundation (NSF) IOS-2019400NHLBI NIH HHS R33 HL154307NHLBI NIH HHS R61 HL154307NIGMS NIH HHS T32 GM008620NINDS NIH HHS DP2 NS122550NINDS NIH HHS F31 NS118845NINDS NIH HHS P01 NS083513NINDS NIH HHS R01 NS119829NINDS NIH HHS T32 NS082174U.S. Department of Health & Human Services | National Institutes of Health (NIH) R61/R33 HL154307
6 · The paper itself

Abstract

Neural stem and progenitor cell (NSPC) and vessel-forming endothelial cell (EC) communication throughout development and adulthood is vital for normal brain function. However, much remains unclear regarding coordinated regulation of these cells, particularly in humans. We find that contact with hECs increases hNSPC type B cells, which are GFAP-expressing adult NSPCs in the subventricular zone (SVZ), leading to generation of a human type B single-cell RNA sequencing (scRNAseq) dataset. Differential gene expression demonstrates an increase in Notch downstream mediators in type B hNSPCs after hEC contact. Blocking hNSPC Notch signaling, and reducing hEC expression of the Notch ligand DLL4, abrogates the effect of hECs on type B hNSPCs. We identify S100A6 and LeX as human type B cell markers, and analysis of the postnatal human SVZ confirms co-expression of GFAP, SOX2, S100A6, LeX and PROM1 in type B cells. Sites of contact are identified between type B hNSPCs and vasculature in the SVZ, providing evidence of human type B cell contact with hECs in the postnatal human brain. Thus, hEC contact promotes human type B cells via Notch signaling and these cells are in contact in stem cell niches in the human brain.

Indexed as

Endothelial CellsNeural Stem CellsReceptors, NotchSignal TransductionAdaptor Proteins, Signal TransducingBrainCalcium-Binding ProteinsCell CommunicationGlial Fibrillary Acidic ProteinHumansLateral VentriclesPhenotypeSingle-Cell AnalysisAdaptor Proteins, Signal TransducingCalcium-Binding ProteinsDLL4 protein, humanGFAP protein, humanGlial Fibrillary Acidic ProteinReceptors, Notch

Identifiers

PMID40447618
PMCPMC12125299

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.