Evidence map›Paper›PMID 41546116›Full record

ArticleFluids and barriers of the CNS2026

Notch signaling activation reduces vesicular endocytosis in human pluripotent stem cell-derived CNS-like endothelial cells.

Sarah M Boutom, Luke D Walsh, Maxwell M Herman, Yunfeng Ding, Fatemeh Yaghoobi Hashjin, Benjamin K August, Eric V Shusta, Sean P Palecek

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Fluids and barriers of the CNS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Sarah M BoutomDepartment of Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, USA.
Luke D WalshDepartment of Chemical and Biological Engineering, University of Wisconsin - Madison, Madison, WI, USA.
Maxwell M HermanDepartment of Biology, University of Wisconsin - Madison, Madison, WI, USA.
Yunfeng DingDepartment of Chemical and Biological Engineering, University of Wisconsin - Madison, Madison, WI, USA.
Fatemeh Yaghoobi HashjinDepartment of Chemical and Biological Engineering, University of Wisconsin - Madison, Madison, WI, USA.
Benjamin K AugustElectron Microscopy Facility, University of Wisconsin - Madison, Madison, WI, USA.
Eric V ShustaDepartment of Chemical and Biological Engineering, University of Wisconsin - Madison, Madison, WI, USA. eshusta@wisc.edu.
Sean P PalecekDepartment of Chemical and Biological Engineering, University of Wisconsin - Madison, Madison, WI, USA. sppalecek@wisc.edu.

Funding

Integrated Training For Physician-ScientistsT32GM140935 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Anna Huttenlocher, Jeniel E Nett · 2021 to 2026
$6.5M
Identifying the role of notch3 in brain pericyte function in health and Alzheimer's diseaseRF1NS132441 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI DANEMAN, RICHARD, PALECEK, SEAN P · 2023 to 2023
$1.8M
Mechanisms of Shear Induction of Blood-Brain Barrier Phenotypes in Human iPSC-derived Brain Endothelial ProgenitorsR01NS107461 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI PALECEK, SEAN P · 2019 to 2023
$1.7M
NIGMS NIH HHS T32 GM140935NIH HHS R01NS107461NIH HHS RF1NS132441NIH HHS T32GM140935NINDS NIH HHS R01 NS107461NINDS NIH HHS RF1 NS132441
6 · The paper itself

Abstract

backgroundMechanisms guiding the induction of blood-brain barrier (BBB) properties in central nervous system (CNS) endothelial cells during human development are incompletely understood. For example, there is a limited understanding of signaling pathways that influence the unique property of low vesicular endocytosis and transcytosis in brain microvascular endothelial cells (BMECs) relative to peripheral endothelial cells. Mouse studies suggest the importance of BBB-relevant developmental pathways, including Wnt and Notch signaling, for the induction of this BBB feature in developing BMECs.

methodsTo explore induction of reduced vesicular endocytosis and transcytosis in human in vitro model of the BBB, we used human pluripotent stem cell (hPSC)-derived endothelial progenitor cells (EPCs) in which Wnt/β-catenin signaling was activated to generate hPSC-derived CNS-like ECs (hPSC-CECs). We assessed the effects of Notch signaling through overexpression of the Notch1 receptor intracellular domain (N1ICD).

resultsN1ICD overexpression in hPSC-CECs resulted in upregulation of GLUT-1, a BBB-enriched glucose transporter, and decreased expression of both PLVAP and caveolin-1, two vesicular endocytosis-associated proteins. The combination of Wnt/β-catenin activation and N1ICD overexpression resulted in fewer vesicles and reduced albumin uptake.

conclusionThese findings indicate that Notch signaling reduces vesicular endocytosis and transcytosis in a human model of the developing BBB and contribute to our understanding of how Notch signaling induces these specific BBB properties in this model of human CNS EC development.

Indexed as

Blood-Brain BarrierEndocytosisEndothelial CellsPluripotent Stem CellsReceptor, Notch1Receptors, NotchSignal TransductionCaveolin 1Cells, CulturedGlucose Transporter Type 1HumansWnt Signaling PathwayCaveolin 1Glucose Transporter Type 1NOTCH1 protein, humanReceptor, Notch1Receptors, NotchCaveolaeEndocytosisEndothelial cellsNotch signalingVesicles

Identifiers

PMID41546116
PMCPMC12874909

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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.