Evidence map›Paper›PMID 37284748›Full record

ArticleeLife2023

Combined lineage tracing and scRNA-seq reveals unexpected first heart field predominance of human iPSC differentiation.

Francisco X Galdos, Carissa Lee, Soah Lee, Sharon Paige, William Goodyer, Sidra Xu, Tahmina Samad, Gabriela V Escobar, Adrija Darsha, Aimee Beck and 3 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

34 citing papers in PubMed, 44 citations in OpenAlex.

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  5. PARROT: Phase-Altering Regulatory Rewiring Over Time.bioRxiv : the preprint server for biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 4 countries.

Francisco X GaldosStanford Cardiovascular Institute, Stanford University, Stanford, United States.ORCID 0000-0002-7985-4521
Carissa LeeStanford Cardiovascular Institute, Stanford University, Stanford, United States.
Soah LeeDepartment of Pharmacy, Sungkyunkwan University, Stanford, United States.
Sharon PaigeStanford Cardiovascular Institute, Stanford University, Stanford, United States.
William GoodyerStanford Cardiovascular Institute, Stanford University, Stanford, United States.
Sidra XuStanford Cardiovascular Institute, Stanford University, Stanford, United States.
Tahmina SamadStanford Cardiovascular Institute, Stanford University, Stanford, United States.
Gabriela V EscobarStanford Cardiovascular Institute, Stanford University, Stanford, United States.
Adrija DarshaSchool of Medicine, University of California, San Diego, San Diego, United States.
Aimee BeckStanford Cardiovascular Institute, Stanford University, Stanford, United States.
Rasmus O BakDepartment of Biomedicine, Aarhus University, Aarhus C, Denmark.ORCID 0000-0002-7383-0297
Matthew H PorteusStanford Cardiovascular Institute, Stanford University, Stanford, United States.ORCID 0000-0002-3850-4648
Sean M WuStanford Cardiovascular Institute, Stanford University, Stanford, United States.ORCID 0000-0002-0000-3821
Cardiovascular Institute of the South · USAarhus University · DKSungkyunkwan University · KRUniversity of California San Diego · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
From proteins to cells to tissues: A multi-scale assessment of biomechanical regulation by the myosin molecular motorRM1GM131981 · NIGMS · STANFORD UNIVERSITY · PI BERNSTEIN, DANIEL, MACK, DAVID LEE · 2019 to 2023
$10.3M
Understanding the Mechanisms of Ventricular Dysfunction in Hypoplastic Left Heart SyndromeF30HL149152 · NHLBI · STANFORD UNIVERSITY · PI GALDOS, FRANCISCO XAVIER · 2019 to 2021
$109k
NHLBI NIH HHS F30 HL149152NIGMS NIH HHS RM1 GM131981NIGMS NIH HHS T32 GM007365
6 · The paper itself

Abstract

During mammalian development, the left and right ventricles arise from early populations of cardiac progenitors known as the first and second heart fields, respectively. While these populations have been extensively studied in non-human model systems, their identification and study in vivo human tissues have been limited due to the ethical and technical limitations of accessing gastrulation-stage human embryos. Human-induced pluripotent stem cells (hiPSCs) present an exciting alternative for modeling early human embryogenesis due to their well-established ability to differentiate into all embryonic germ layers. Here, we describe the development of a TBX5/MYL2 lineage tracing reporter system that allows for the identification of FHF- progenitors and their descendants including left ventricular cardiomyocytes. Furthermore, using single-cell RNA sequencing (scRNA-seq) with oligonucleotide-based sample multiplexing, we extensively profiled differentiating hiPSCs across 12 timepoints in two independent iPSC lines. Surprisingly, our reporter system and scRNA-seq analysis revealed a predominance of FHF differentiation using the small molecule Wnt-based 2D differentiation protocol. We compared this data with existing murine and 3D cardiac organoid scRNA-seq data and confirmed the dominance of left ventricular cardiomyocytes (>90%) in our hiPSC-derived progeny. Together, our work provides the scientific community with a powerful new genetic lineage tracing approach as well as a single-cell transcriptomic atlas of hiPSCs undergoing cardiac differentiation.

Indexed as

Induced Pluripotent Stem CellsAnimalsCell DifferentiationHumansMammalsMiceMyocytes, CardiacSingle-Cell Gene Expression AnalysisTranscriptomecardiac developmentcardiomyocytedevelopmental biologygenetic engineeringhumanlineage tracingmousepluripotent stem cellsregenerative medicinestem cellstranscription factors

Identifiers

PMID37284748
PMCPMC10348749
OpenAlexW4379600929

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.