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
Jiejia XuKenneth R Chien

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 meso...Continue Reading

References

Nov 14, 1997·Nature Genetics·M GebbiaB Casey
Dec 19, 2003·American Journal of Human Genetics·Stephanie M WareJohn W Belmont
Feb 11, 2005·Nature·Karl-Ludwig LaugwitzKenneth R Chien
May 29, 2007·Nature Biotechnology·Kiichi WatanabeYoshiki Sasai
Sep 13, 2011·The Journal of Biological Chemistry·Rasoul PourebrahimSabine Tejpar
May 31, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xiaojun LianSean P Palecek
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Feb 28, 2013·Cellular and Molecular Life Sciences : CMLS·Rob HoutmeyersRuth Arkell
Dec 18, 2013·Science·Tim WangEric S Lander
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
Dec 29, 2013·Stem Cell Reports·Matthew J BirketChristine L Mummery
Jan 5, 2014·Nature Protocols·Simone PicelliRickard Sandberg
Mar 4, 2014·Genesis : the Journal of Genetics and Development·Kristen S BarrattRuth M Arkell
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Feb 24, 2015·Molecular Cell·Zhuojuan LuoAli Shilatifard
Mar 10, 2015·Nature Methods·Daehwan KimSteven L Salzberg
Apr 14, 2016·Molecular Cell·Sergio RuizOscar Fernandez-Capetillo
Mar 28, 2017·Nature Methods·Vladimir Yu KiselevMartin Hemberg
Apr 8, 2017·Science·Pengpeng BiEric N Olson
Apr 3, 2018·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kylie S FooKenneth R Chien
Oct 31, 2018·Stem Cells·Jiejia XuKenneth R Chien
Dec 12, 2018·Nature Biotechnology·Etienne BechtEvan W Newell
Jun 11, 2019·Cell·Tim StuartRahul Satija
Nov 2, 2019·Briefings in Bioinformatics·Xinlei ZhaoJue Fan

❮ Previous
Next ❯

Citations

Apr 30, 2021·Development·Ersin AkinciRichard I Sherwood

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
PCR
FACS
transfections
chemical stress
flow cytometry
Flow
MDS

Software Mentioned

bowtie
Fastq
R package
FlowJo
custom
map
R package edgeR
SingleCellExperiment
package
FeatureCounts

Related Concepts

Related Feeds

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Cardiac Regeneration

Cardiac regeneration enables the repair of irreversibly damaged heart tissue using cutting-edge science, including stem cell and cell-free therapy. Discover the latest research on cardiac regeneration here.

© 2021 Meta ULC. All rights reserved