Single-cell reconstruction of differentiation trajectory reveals a critical role of ETS1 in human cardiac lineage commitment.

Ruan, H; Liao, Y; Ren, Z; Mao, L; Yao, F; Yu, P; Ye, Y; Zhang, Z; Li, S; Xu, H; Liu, J; Diao, L; Zhou, B; Han, L; Wang, L

Single-cell reconstruction of differentiation trajectory reveals a critical role of ETS1 in human cardiac lineage commitment.

Ruan, H Liao, Y Ren, Z Mao, L Yao, F Yu, P Ye, Y Zhang, Z Li, S Xu, H

Liu, J Diao, L Zhou, B Han, L Wang, L

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Publisher:: Springer Nature
Publication Type:: Journal Article
Citation:: BMC Biol, 2019, 17, (1), pp. 89
Issue Date:: 2019-11-13

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Field	Value	Language
dc.contributor.author	Ruan, H
dc.contributor.author	Liao, Y
dc.contributor.author	Ren, Z
dc.contributor.author	Mao, L
dc.contributor.author	Yao, F
dc.contributor.author	Yu, P
dc.contributor.author	Ye, Y
dc.contributor.author	Zhang, Z
dc.contributor.author	Li, S
dc.contributor.author	Xu, H https://orcid.org/0000-0003-1129-5337
dc.contributor.author	Liu, J
dc.contributor.author	Diao, L
dc.contributor.author	Zhou, B
dc.contributor.author	Han, L
dc.contributor.author	Wang, L
dc.date.accessioned	2024-03-12T04:01:47Z
dc.date.available	2019-10-15
dc.date.available	2024-03-12T04:01:47Z
dc.date.issued	2019-11-13
dc.identifier.citation	BMC Biol, 2019, 17, (1), pp. 89
dc.identifier.issn	1741-7007
dc.identifier.issn	1741-7007
dc.identifier.uri	http://hdl.handle.net/10453/176552
dc.description.abstract	BACKGROUND: Cardiac differentiation from human pluripotent stem cells provides a unique opportunity to study human heart development in vitro and offers a potential cell source for cardiac regeneration. Compared to the large body of studies investigating cardiac maturation and cardiomyocyte subtype-specific induction, molecular events underlying cardiac lineage commitment from pluripotent stem cells at early stage remain poorly characterized. RESULTS: In order to uncover key molecular events and regulators controlling cardiac lineage commitment from a pluripotent state during differentiation, we performed single-cell RNA-Seq sequencing and obtained high-quality data for 6879 cells collected from 6 stages during cardiac differentiation from human embryonic stem cells and identified multiple cell subpopulations with distinct molecular features. Through constructing developmental trajectory of cardiac differentiation and putative ligand-receptor interactions, we revealed crosstalk between cardiac progenitor cells and endoderm cells, which could potentially provide a cellular microenvironment supporting cardiac lineage commitment at day 5. In addition, computational analyses of single-cell RNA-Seq data unveiled ETS1 (ETS Proto-Oncogene 1) activation as an important downstream event induced by crosstalk between cardiac progenitor cells and endoderm cells. Consistent with the findings from single-cell analysis, chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) against ETS1 revealed genomic occupancy of ETS1 at cardiac structural genes at day 9 and day 14, whereas ETS1 depletion dramatically compromised cardiac differentiation. CONCLUSION: Together, our study not only characterized the molecular features of different cell types and identified ETS1 as a crucial factor induced by cell-cell crosstalk contributing to cardiac lineage commitment from a pluripotent state, but may also have important implications for understanding human heart development at early embryonic stage, as well as directed manipulation of cardiac differentiation in regenerative medicine.
dc.format	Electronic
dc.language	eng
dc.publisher	Springer Nature
dc.relation.ispartof	BMC Biol
dc.relation.isbasedon	10.1186/s12915-019-0709-6
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	06 Biological Sciences
dc.subject.classification	Developmental Biology
dc.subject.classification	31 Biological sciences
dc.subject.mesh	Cell Differentiation
dc.subject.mesh	Human Embryonic Stem Cells
dc.subject.mesh	Humans
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Proto-Oncogene Mas
dc.subject.mesh	Proto-Oncogene Protein c-ets-1
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Humans
dc.subject.mesh	Cell Differentiation
dc.subject.mesh	Proto-Oncogene Protein c-ets-1
dc.subject.mesh	Human Embryonic Stem Cells
dc.subject.mesh	Proto-Oncogene Mas
dc.subject.mesh	Cell Differentiation
dc.subject.mesh	Human Embryonic Stem Cells
dc.subject.mesh	Humans
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Proto-Oncogene Mas
dc.subject.mesh	Proto-Oncogene Protein c-ets-1
dc.title	Single-cell reconstruction of differentiation trajectory reveals a critical role of ETS1 in human cardiac lineage commitment.
dc.type	Journal Article
utslib.citation.volume	17
utslib.location.activity	England
utslib.for	06 Biological Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Computer Science
utslib.copyright.status	open_access	*
dc.date.updated	2024-03-12T04:01:40Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	17
utslib.citation.issue	1

Abstract:

BACKGROUND: Cardiac differentiation from human pluripotent stem cells provides a unique opportunity to study human heart development in vitro and offers a potential cell source for cardiac regeneration. Compared to the large body of studies investigating cardiac maturation and cardiomyocyte subtype-specific induction, molecular events underlying cardiac lineage commitment from pluripotent stem cells at early stage remain poorly characterized. RESULTS: In order to uncover key molecular events and regulators controlling cardiac lineage commitment from a pluripotent state during differentiation, we performed single-cell RNA-Seq sequencing and obtained high-quality data for 6879 cells collected from 6 stages during cardiac differentiation from human embryonic stem cells and identified multiple cell subpopulations with distinct molecular features. Through constructing developmental trajectory of cardiac differentiation and putative ligand-receptor interactions, we revealed crosstalk between cardiac progenitor cells and endoderm cells, which could potentially provide a cellular microenvironment supporting cardiac lineage commitment at day 5. In addition, computational analyses of single-cell RNA-Seq data unveiled ETS1 (ETS Proto-Oncogene 1) activation as an important downstream event induced by crosstalk between cardiac progenitor cells and endoderm cells. Consistent with the findings from single-cell analysis, chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) against ETS1 revealed genomic occupancy of ETS1 at cardiac structural genes at day 9 and day 14, whereas ETS1 depletion dramatically compromised cardiac differentiation. CONCLUSION: Together, our study not only characterized the molecular features of different cell types and identified ETS1 as a crucial factor induced by cell-cell crosstalk contributing to cardiac lineage commitment from a pluripotent state, but may also have important implications for understanding human heart development at early embryonic stage, as well as directed manipulation of cardiac differentiation in regenerative medicine.

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http://hdl.handle.net/10453/176552