ArticleStem cells (Dayton, Ohio)2020
Genome-wide CRISPR screen identifies ZIC2 as an essential gene that controls the cell fate of early mesodermal precursors to human heart progenitors.
Article in Stem cells (Dayton, Ohio), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- CRISPR and the Future of Cardiac Disease Therapy: A New Genetic Frontier.International journal of molecular sciences · 2026Review
- A chemical epigenetic tool to probe site-specific DNA-binding protein complexes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A genome-wide, CRISPR-based screen reveals new requirements for translation initiation and ubiquitination in driving adipogenic fate change.Genes & development · 2025Article
- Engineered Cardiac Tissues as a Platform for CRISPR-Based Mitogen Discovery.Advanced healthcare materials · 2025Article
- Single-cell RNA sequencing reveals key regulators and differentiation trajectory of iPSC-derived cardiomyocytes.Scientific reports · 2024Article
- ZIC2 and ZIC3 promote SWI/SNF recruitment to safeguard progression towards human primed pluripotency.Nature communications · 2024Article
- Genome-scale CRISPR-Cas9 screening in stem cells: theories, applications and challenges.Stem cell research & therapy · 2024Review
- Unveiling the hidden role of the interaction between CD36 and FcγRIIb: implications for autoimmune disorders.Cellular & molecular biology letters · 2024Article
- CRISPR-based functional genomics screening in human-pluripotent-stem-cell-derived cell types.Cell genomics · 2023Review
- Article
- CRISPR screening in cardiovascular research.Frontiers in cell and developmental biology · 2023Review
- Robust genome editing via modRNA-based Cas9 or base editor in human pluripotent stem cells.Cell reports methods · 2022Article
- Human-gained heart enhancers are associated with species-specific cardiac attributes.Nature cardiovascular research · 2022Article
- The use of new CRISPR tools in cardiovascular research and medicine.Nature reviews. Cardiology · 2022Review
- Mesp1 controls the chromatin and enhancer landscapes essential for spatiotemporal patterning of early cardiovascular progenitors.Nature cell biology · 2022Article
- Genome-wide CRISPR/Cas9 screening in human iPS derived cardiomyocytes uncovers novel mediators of doxorubicin cardiotoxicity.Scientific reports · 2021Article
- Using CRISPR to understand and manipulate gene regulation.Development (Cambridge, England) · 2021Review
- Genome-wide CRISPR screen identifies ZIC2 as an essential gene that controls the cell fate of early mesodermal precursors to human heart progenitors.Stem cells (Dayton, Ohio) · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
Cardiac progenitor formation is one of the earliest committed steps of human cardiogenesis and requires the cooperation of multiple gene sets governed by developmental signaling cascades. To determine the key regulators for cardiac progenitor formation, we have developed a two-stage genome-wide CRISPR-knockout screen. We mimicked the progenitor formation process by differentiating human pluripotent stem cells (hPSCs) into cardiomyocytes, monitored by two distinct stage markers of early cardiac mesodermal formation and commitment to a multipotent heart progenitor cell fate: MESP1 and ISL1, respectively. From the screen output, we compiled a list of 15 candidate genes. After validating seven of them, we identified ZIC2 as an essential gene for cardiac progenitor formation. ZIC2 is known as a master regulator of neurogenesis. hPSCs with ZIC2 mutated still express pluripotency markers. However, their ability to differentiate into cardiomyocytes was greatly attenuated. RNA-Seq profiling of the ZIC2-mutant cells revealed that the mutants switched their cell fate alternatively to the noncardiac cell lineage. Further, single cell RNA-seq analysis showed the ZIC2 mutants affected the apelin receptor-related signaling pathway during mesoderm formation. Our results provide a new link between ZIC2 and human cardiogenesis and document the potential power of a genome-wide unbiased CRISPR-knockout screen to identify the key steps in human mesoderm precursor cell- and heart progenitor cell-fate determination during in vitro hPSC cardiogenesis.
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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.