Evidence map›Paper›PMID 35488063›Full record

ArticleCommunications biology2022

Computational profiling of hiPSC-derived heart organoids reveals chamber defects associated with NKX2-5 deficiency.

Wei Feng, Hannah Schriever, Shan Jiang, Abha Bais, Haodi Wu, Dennis Kostka, Guang Li

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

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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 at 1 institution in 1 country.

Wei Feng *Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-5605-0811
Hannah Schriever *Joint Carnegie Mellon, University of Pittsburgh Ph.D. Program in Computational Biology, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-9459-5548
Shan JiangDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Abha BaisDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-5910-1306
Haodi WuVascular Medicine Institute Division of Cardiology, University of Pittsburgh Department of Medicine, Pittsburgh, PA, USA.
Dennis KostkaDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. kostka@pitt.edu.ORCID http://orcid.org/0000-0002-1460-5487
Guang LiDepartment of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. guangli@pitt.edu.ORCID http://orcid.org/0000-0002-8546-2364
University of Pittsburgh · US

Funding

Integrated Interdisciplinary, inter-university PhD Program Computational Biology (T32)T32EB009403 · NIBIB · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAHAR, IVET, BAR-JOSEPH, ZIV · 2009 to 2023
$4.4M
Generation of four-chambered hearts through organoid fusionsDP2HL163745 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LI, GUANG · 2021 to 2024
$2.4M
Cellular and Molecular Mechanisms of Atrial Cardiomyocyte Lineage Commitment R00HL133472 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LI, GUANG · 2019 to 2021
$750k
Epigenetic regulation of PDE signaling in dilated cardiomyopathyR00HL133473 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WU, HAODI · 2021 to 2023
$747k
NHLBI NIH HHS DP2 HL163745NHLBI NIH HHS R00 HL133472NHLBI NIH HHS R00 HL133473NIBIB NIH HHS T32 EB009403
6 · The paper itself

Abstract

Heart organoids have the potential to generate primary heart-like anatomical structures and hold great promise as in vitro models for cardiac disease. However, their properties have not yet been fully studied, which hinders their wide spread application. Here we report the development of differentiation systems for ventricular and atrial heart organoids, enabling the study of heart diseases with chamber defects. We show that our systems generate chamber-specific organoids comprising of the major cardiac cell types, and we use single cell RNA sequencing together with sample multiplexing to characterize the cells we generate. To that end, we developed a machine learning label transfer approach leveraging cell type, chamber, and laterality annotations available for primary human fetal heart cells. We then used this model to analyze organoid cells from an isogeneic line carrying an Ebstein's anomaly associated genetic variant in NKX2-5, and we successfully recapitulated the disease's atrialized ventricular defects. In summary, we have established a workflow integrating heart organoids and computational analysis to model heart development in normal and disease states.

Indexed as

Induced Pluripotent Stem CellsOrganoidsHeartHeart VentriclesHomeobox Protein Nkx-2.5HumansOrganogenesisHomeobox Protein Nkx-2.5NKX2-5 protein, human

Identifiers

PMID35488063
PMCPMC9054831
OpenAlexW4225259023

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.