Evidence map›Paper›PMID 31591580›Full record

ArticleNature methods2019

Engineering of human brain organoids with a functional vascular-like system.

Bilal Cakir, Yangfei Xiang, Yoshiaki Tanaka, Mehmet H Kural, Maxime Parent, Young-Jin Kang, Kayley Chapeton, Benjamin Patterson, Yifan Yuan, Chang-Shun He and 12 more

Abstract read
In one paragraph

Article in Nature methods, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 577 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
577citing papers in PubMed, 3 pooled it
–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

577 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Pooled it
  4. Review
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  6. Article
  7. Article
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  9. Review
  10. Article
  11. Review
  12. Using Brain Organoids to Explore Human Neurobiology.Cellular and molecular neurobiology · 2026
    Review
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  17. Article
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517 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

22 authors.

Bilal Cakir *Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-4610-0317
Yangfei Xiang *Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Yoshiaki TanakaDepartment of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Mehmet H KuralDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT, USA.
Maxime ParentDepartment of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.
Young-Jin KangDepartment of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Kayley ChapetonDepartment of Electrical Engineering, University of Bridgeport, Bridgeport, CT, USA.
Benjamin PattersonDepartment of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Yifan YuanDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT, USA.
Chang-Shun HeDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Micha Sam B RaredonDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT, USA.
Jake DengelegiDepartment of Biomedical Engineering, University of Bridgeport, Bridgeport, CT, USA.
Kun-Yong KimDepartment of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Pingnan SunDepartment of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Mei ZhongDepartment of Cell Biology, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Sangho LeeDepartment of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA.
Prabir PatraDepartment of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Fahmeed HyderDepartment of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.
Laura E NiklasonDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT, USA.
Sang-Hun LeeDepartment of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.ORCID http://orcid.org/0000-0001-8880-2785
Young-Sup YoonDepartment of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA.
In-Hyun ParkDepartment of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA. inhyun.park@yale.edu.ORCID http://orcid.org/0000-0001-7748-1293

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007499 · NIGMS · YALE UNIVERSITY · PI CARLSON, JOHN R, REINKE, VALERIE J · 1985 to 2022
$13.9M
Telemedicine CoreP30GM110702 · NIGMS · UNIV OF ARKANSAS FOR MED SCIS · PI HALL, WHIT · 2014 to 2018
$6.1M
Energetics of Neuronal Populations by fMRIR01MH067528 · NIMH · YALE UNIVERSITY · PI HYDER, DEWAN SYED FAHMEED · 2002 to 2021
$5.9M
Biologically Selective Drug-Eluting StentR01HL148819 · NHLBI · YALE UNIVERSITY · PI SALTZMAN, WILLIAM · 2019 to 2022
$2.7M
Effects of reprogrammed and engineered MSCs on diabetic complicationsDP3DK108245 · NIDDK · EMORY UNIVERSITY · PI YOON, YOUNG-SUP · 2015 to 2016
$2.6M
Extracellular pH mapping as therapeutic readout of drug delivery in glioblastomaR01EB023366 · NIBIB · YALE UNIVERSITY · PI HYDER, DEWAN SYED FAHMEED · 2017 to 2020
$2.5M
Hyaluronan Coatings for Engineered VesselsR01HL127386 · NHLBI · YALE UNIVERSITY · PI NIKLASON, LAURA E · 2016 to 2019
$2.5M
Bone and Breast Cancer Molecular InteractionsR01CA203011 · NCI · YALE UNIVERSITY · PI LEE, FRANCIS YOUNG-IN · 2016 to 2020
$2.3M
Cardiac Revascularization with Direct Reprogramming ApproachesR01HL150887 · NHLBI · EMORY UNIVERSITY · PI YOON, YOUNG-SUP · 2020 to 2023
$1.8M
Brain microRNA-mRNA regulatory networks and alcohol use disordersR01AA025080 · NIAAA · YALE UNIVERSITY · PI ZHANG, HUIPING · 2016 to 2020
$1.7M
NCATS NIH HHS UL1 TR001863NCI NIH HHS R01 CA203011NHLBI NIH HHS R01 HL127386NHLBI NIH HHS R01 HL127759NHLBI NIH HHS R01 HL129511NHLBI NIH HHS R01 HL148819NHLBI NIH HHS R01 HL150887NIAAA NIH HHS R01 AA025080NIBIB NIH HHS R01 EB023366NIBIB NIH HHS R21 EB024889NIDDK NIH HHS DP3 DK108245NIGMS NIH HHS P30 GM110702NIGMS NIH HHS R01 GM111667NIGMS NIH HHS T32 GM007205NIGMS NIH HHS T32 GM007499NIMH NIH HHS R01 MH067528
6 · The paper itself

Abstract

Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide a platform to study human brain development and diseases in complex three-dimensional tissue. However, current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. We engineered hESCs to ectopically express human ETS variant 2 (ETV2). ETV2-expressing cells in hCOs contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vasculature-like structures resulted in enhanced functional maturation of organoids. We found that vascularized hCOs (vhCOs) acquired several blood-brain barrier characteristics, including an increase in the expression of tight junctions, nutrient transporters and trans-endothelial electrical resistance. Finally, ETV2-induced endothelium supported the formation of perfused blood vessels in vivo. These vhCOs form vasculature-like structures that resemble the vasculature in early prenatal brain, and they present a robust model to study brain disease in vitro.

Indexed as

AnimalsBlood-Brain BarrierBrainCells, CulturedHuman Embryonic Stem CellsHumansMiceOrganoidsSingle-Cell AnalysisTissue EngineeringTranscription FactorsETV2 protein, humanTranscription Factors

Identifiers

PMID31591580
PMCPMC6918722

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.