Evidence map›Paper›PMID 33542154›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate.

Tyler M Lu, Sean Houghton, Tarig Magdeldin, José Gabriel Barcia Durán, Andrew P Minotti, Amanda Snead, Andrew Sproul, Duc-Huy T Nguyen, Jenny Xiang, Howard A Fine and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 2 pooled it
14.4field-weighted citation impact, top 1% of its field
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

128 citing papers in PubMed, 2 syntheses or guidelines pooled it, 219 citations in OpenAlex.

  1. Pooled it
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  7. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
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  19. Engineered 3D immuno-glial-neurovascular human miBrain model.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Article

68 more citing papers are in PubMed but not listed here.

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

16 authors at 4 institutions in 1 country.

Tyler M LuAnsary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0003-4973-0840
Sean HoughtonAnsary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065.
Tarig MagdeldinDepartment of Neurology and the Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY 10065.
José Gabriel Barcia DuránAnsary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0003-4764-5503
Andrew P MinottiDevelopmental Biology, the Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
Amanda SneadDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032.
Andrew SproulDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032.
Duc-Huy T NguyenAnsary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065.
Jenny XiangGenomics Resources Core Facility, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0003-0484-2769
Howard A FineDepartment of Neurology and the Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY 10065.
Zev RosenwaksRonald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10065.
Lorenz StuderThe Biochemistry, Structural Biology, Cell Biology, Developmental Biology and Molecular Biology Allied Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065.ORCID 0000-0003-0741-7987
Shahin RafiiAnsary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065.
Dritan AgalliuDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032.ORCID 0000-0002-5375-4143
David RedmondAnsary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065; dar2042@med.cornell.edu ral2020@med.cornell.edu.
Raphaël LisAnsary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10065; dar2042@med.cornell.edu ral2020@med.cornell.edu.ORCID 0000-0003-2541-4798
Cornell University · USColumbia University Irving Medical Center · USNewYork–Presbyterian Hospital · USMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Genetic Epidemiology of Cerebrovascular Factors in Alzheimer's DiseaseRF1AG054023 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2016 to 2018
$8.9M
Human Brain Cancer, Rather than Brain Cancer Cells, on a PlateDP1CA228040 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI FINE, HOWARD A. · 2017 to 2021
$5.9M
Cellular and humoral immune mechanisms underlying neurovascular dysfunction in autoimmune encephalitisR01MH112849 · NIMH · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI AGALLIU, DRITAN, CUTFORTH, TYLER · 2017 to 2020
$2.1M
miR regulation of the neurovasculature function in health and diseaseR01NS107344 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PEDERSEN, IRENE MUNK · 2018 to 2021
$1.7M
Developing a microfluidic human neurovascular unit system to investigate genetic and age-related risk factors in Alzheimer's diseaseR01AG078352 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Dritan Agalliu, Andrew Alexander Sproul · 2025 to 2026
$837k
The role of autophagy in the neurovascular unit for the physiological response to stress.R21NS118891 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI AGALLIU, DRITAN, YAMAMOTO, AI · 2020 to 2020
$438k
Loss of nuclear integrity is sufficient to induce age-associated changes and Alzheimer's pathology in hPSC-derived cortical neurons.F31AG067709 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI MINOTTI, ANDREW · 2020 to 2022
$138k
NCI NIH HHS DP1 CA228040NCI NIH HHS P30 CA008748NIA NIH HHS F31 AG067709NIA NIH HHS R01 AG078352NIA NIH HHS RF1 AG054023NIMH NIH HHS R01 MH112849NINDS NIH HHS R01 NS107344NINDS NIH HHS R21 NS118891
6 · The paper itself

Abstract

Cells derived from pluripotent sources in vitro must resemble those found in vivo as closely as possible at both transcriptional and functional levels in order to be a useful tool for studying diseases and developing therapeutics. Recently, differentiation of human pluripotent stem cells (hPSCs) into brain microvascular endothelial cells (ECs) with blood-brain barrier (BBB)-like properties has been reported. These cells have since been used as a robust in vitro BBB model for drug delivery and mechanistic understanding of neurological diseases. However, the precise cellular identity of these induced brain microvascular endothelial cells (iBMECs) has not been well described. Employing a comprehensive transcriptomic metaanalysis of previously published hPSC-derived cells validated by physiological assays, we demonstrate that iBMECs lack functional attributes of ECs since they are deficient in vascular lineage genes while expressing clusters of genes related to the neuroectodermal epithelial lineage (Epi-iBMEC). Overexpression of key endothelial ETS transcription factors (

Indexed as

AnimalsBlood-Brain BarrierBrainCell DifferentiationCell LineCellular ReprogrammingEndothelium, VascularGene ExpressionHumansMiceMice, Inbred StrainsPluripotent Stem CellsProto-Oncogene Protein c-fli-1Single-Cell AnalysisTranscriptional Regulator ERGTranscription FactorsERG protein, humanETV2 protein, humanFLI1 protein, humanProto-Oncogene Protein c-fli-1Transcriptional Regulator ERGTranscription Factorsblood–brain barriercellular identityendothelial cellsinduced pluripotentsingle-cell RNA sequencing

Identifiers

PMID33542154
PMCPMC7923590
OpenAlexW3128452637

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.