Evidence map›Paper›PMID 36039869›Full record

ArticleDevelopment (Cambridge, England)2022

Stable iPSC-derived NKX2-1+ lung bud tip progenitor organoids give rise to airway and alveolar cell types.

Renee F C Hein, Ansley S Conchola, Alexis S Fine, Zhiwei Xiao, Tristan Frum, Lindy K Brastrom, Mayowa A Akinwale, Charlie J Childs, Yu-Hwai Tsai, Emily M Holloway and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Development (Cambridge, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.3field-weighted citation impact, top 6% 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

27 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Mechanosensing Pathways in the Progression of Pulmonary Fibrosis.Current opinion in biomedical engineering · 2025
    Article
  6. Article
  7. Review
  8. Cell Population-resolved Multiomics Atlas of the Developing Lung.American journal of respiratory cell and molecular biology · 2025
    Article
  9. Lung stem cells and respiratory epithelial chimerism in transplantation.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
  10. Article
  11. Review
  12. Review
  13. Guidelines for Manufacturing and Application of Organoids: Lung.International journal of stem cells · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
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

14 authors at 2 institutions in 1 country.

Renee F C HeinDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-1614-2420
Ansley S ConcholaProgram in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-2385-6712
Alexis S FineDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Zhiwei XiaoDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Tristan FrumDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0003-3452-8762
Lindy K BrastromDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Mayowa A AkinwaleDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Charlie J ChildsDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-4480-2625
Yu-Hwai TsaiDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Emily M HollowayDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Sha HuangDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
John MahoneyTherapeutics Lab, Cystic Fibrosis Foundation, Lexington, MA 02421, USA.ORCID 0000-0001-9414-9110
Idse HeemskerkDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-8861-7712
Jason R SpenceDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0001-7869-3992
University of Michigan · USCystic Fibrosis Foundation · US

Funding

MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
Tissue Engineering and RegenerationT32DE007057 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID H. KOHN · 1985 to 2026
$17.3M
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
Cellular and Molecular Biology at MichiganT32GM145470 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Chadwick Brenner · 2022 to 2026
$4.1M
Cellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6M
Characterization of a New Epithelial Cell in the Developing Human LungF30HL156474 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CONCHOLA, ANSLEY CORINNE SEMACK · 2021 to 2023
$137k
Investigating the role of mesenchymal R-Spondin2 during human lung developmentF31HL152531 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CONWAY, RENEE FRANCES · 2020 to 2022
$110k
Investigating organ-specific patterning of the vasculature during human developmentF31HL146162 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HOLLOWAY, EMILY MARIE · 2019 to 2020
$74k
NHLBI NIH HHS F30 HL156474NHLBI NIH HHS F31 HL146162NHLBI NIH HHS F31 HL152531NHLBI NIH HHS R01 HL119215NIDCR NIH HHS T32 DE007057NIGMS NIH HHS T32 GM007863NIGMS NIH HHS T32 GM145304NIGMS NIH HHS T32 GM145470
6 · The paper itself

Abstract

Bud tip progenitors (BTPs) in the developing lung give rise to all epithelial cell types found in the airways and alveoli. This work aimed to develop an iPSC organoid model enriched with NKX2-1+ BTP-like cells. Building on previous studies, we optimized a directed differentiation paradigm to generate spheroids with more robust NKX2-1 expression. Spheroids were expanded into organoids that possessed NKX2-1+/CPM+ BTP-like cells, which increased in number over time. Single cell RNA-sequencing analysis revealed a high degree of transcriptional similarity between induced BTPs (iBTPs) and in vivo BTPs. Using FACS, iBTPs were purified and expanded as induced bud tip progenitor organoids (iBTOs), which maintained an enriched population of bud tip progenitors. When iBTOs were directed to differentiate into airway or alveolar cell types using well-established methods, they gave rise to organoids composed of organized airway or alveolar epithelium, respectively. Collectively, iBTOs are transcriptionally and functionally similar to in vivo BTPs, providing an important model for studying human lung development and differentiation.

Indexed as

Induced Pluripotent Stem CellsPluripotent Stem CellsAlveolar Epithelial CellsCell DifferentiationHumansLungOrganoidsThyroid Nuclear Factor 1NKX2-1 protein, humanThyroid Nuclear Factor 1Bud tip progenitorHuman pluripotent stem cellLung organoidSingle cell RNA sequencing

Identifiers

PMID36039869
PMCPMC9534489
OpenAlexW4293577024

What OpenQuestion holds

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LicenceCC BY
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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.