Evidence map›Paper›PMID 30664680›Full record

ArticleNature protocols2019

Generation of lung organoids from human pluripotent stem cells in vitro.

Alyssa J Miller, Briana R Dye, Daysha Ferrer-Torres, David R Hill, Arend W Overeem, Lonnie D Shea, Jason R Spence

Abstract read
In one paragraph

Article in Nature protocols, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
259citing papers in PubMed, 2 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

259 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  10. Preclinical human models of primary ciliary dyskinesia.European respiratory review : an official journal of the European Respiratory Society · 2026
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199 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

7 authors.

Alyssa J MillerProgram in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Briana R DyeDepartment of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA.
Daysha Ferrer-TorresDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
David R HillDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Arend W OvereemDepartment of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Lonnie D SheaDepartment of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA.
Jason R SpenceProgram in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, USA. spencejr@umich.edu.ORCID http://orcid.org/0000-0001-7869-3992

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Scott Soleimanpour · 2013 to 2026
$24.3M
CELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8M
TRAINING PROGRAM IN ORGANOGENESIST32HD007505 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PASCA DI MAGLIANO, MARINA, SPENCE, JASON · 1997 to 2021
$6.9M
Supplement to a Hox-Wnt-Sox signaling axis regulates lung development, patterning and branchingR01HL119215 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SPENCE, JASON · 2013 to 2021
$4.2M
Mechanisms of basal cell differentiation during murine and human lung developmentF31HL142197 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MILLER, ALYSSA JANE · 2018 to 2019
$57k
NHLBI NIH HHS F31 HL142197NHLBI NIH HHS R01 HL119215NICHD NIH HHS T32 HD007505NIDDK NIH HHS P30 DK020572NIGMS NIH HHS T32 GM007315NIH HHS R01HL119215
6 · The paper itself

Abstract

The lung epithelium is derived from the endodermal germ layer, which undergoes a complex series of endoderm-mesoderm-mediated signaling events to generate the final arborized network of conducting airways (bronchi, bronchioles) and gas-exchanging units (alveoli). These stages include endoderm induction, anterior-posterior and dorsal-ventral patterning, lung specification, lung budding, branching morphogenesis, and, finally, maturation. Here we describe a protocol that recapitulates several of these milestones in order to differentiate human pluripotent stem cells (hPSCs) into ventral-anterior foregut spheroids and further into two distinct types of organoids: human lung organoids and bud tip progenitor organoids. The resulting human lung organoids possess cell types and structures that resemble the bronchi/bronchioles of the developing human airway surrounded by lung mesenchyme and cells expressing alveolar-cell markers. The bud tip progenitor organoids possess a population of highly proliferative multipotent cells with in vitro multilineage differentiation potential and in vivo engraftment potential. Human lung organoids can be generated from hPSCs in 50-85 d, and bud tip progenitor organoids can be generated in 22 d. The two hPSC-derived models presented here have been benchmarked with human fetal tissue and found to be representative of human fetal-like tissue. The bud tip progenitor organoids are thus ideal for exploring epithelial fate decisions, while the human lung organoids can be used to model epithelial-mesenchymal cross-talk during human lung development. In addition to their applications in developmental biology, human lung organoids and bud tip progenitor organoids may be implemented in regenerative medicine, tissue engineering, and pharmaceutical safety and efficacy testing.

Indexed as

Cell Culture TechniquesBenchmarkingBiomarkersCell DifferentiationCell LineCell LineageCell ProliferationEpithelial CellsHumansLungOrganogenesisOrganoidsPluripotent Stem CellsRegenerative MedicineRespiratory MucosaTissue EngineeringBiomarkers

Identifiers

PMID30664680
PMCPMC6531049

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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.