Functional Heterogeneity within the Developing Zebrafish Epicardium

Weinberger, Michael; Simões, Filipa C.; Patient, Roger; Sauka‐Spengler, Tatjana; Riley, Paul R.

doi:10.1016/j.devcel.2020.01.023

Cited by 55 publications

(57 citation statements)

References 90 publications

(107 reference statements)

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“…Epicardial cells also arrive in the heart after chamber defects are evident in the 48 hpf mutants; epicardial cells emerge at around 55 hpf and migrate to and attach to the myocardium by 72 hpf 33 . Interestingly, Sema3fb is important in zebrafish epicardial development at later stages: by 5 dpf sema3fb is expressed by tbx18 + epicardial cells and not cardiomyocytes, and Sema3fb regulates epicardial cell numbers in the bulbus arteriosus 70 . We also saw in mutant hearts the normal arrival of cardiomyocytes from non-heart sources, including from the secondary heart field 64 and CNC 71 .…”

Section: Discussionmentioning

confidence: 99%

Semaphorin3f as an intrinsic regulator of chamber-specific heart development

Halabi

Cechmanek

Hehr

et al. 2021

Preprint

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During development a pool of precursors form a heart with atrial and ventricular chambers that exhibit distinct transcriptional and electrophysiological properties. Normal development of these chambers is essential for full term survival of the fetus, and deviations result in congenital heart defects. The large number of genes that may cause congenital heart defects when mutated, and the genetic variability and penetrance of the ensuing phenotypes, reveals a need to understand the molecular mechanisms that allow for the formation of chamber-specific cardiomyocyte differentiation. We find that in the developing zebrafish heart, mRNA for a secreted Semaphorin (Sema), Sema3fb, is expressed by all cardiomyocytes, whereas mRNA for its receptor Plexina3 (Plxna3) is expressed by ventricular cardiomyocytes. In sema3fb CRISPR zebrafish mutants, ventricular chamber development is impaired; the ventricles of mutants are smaller in size than their wild type siblings, apparently because of differences in cell size and not cell numbers, with ventricular cardiomyocytes failing to undergo normal developmental hypertrophy. Analysis of chamber differentiation indicates defects in chamber specific gene expression at the border between the ventricular and atrial chambers, with spillage of ventricular chamber genes into the atrium, and vice versa, and a failure to restrict bmp4a mRNA to the atrioventricular canal. The disrupted atrioventricular border region in mutants is accompanied by hypoplastic heart chambers and impaired cardiac function. These data suggest a model whereby cardiomyocytes secrete a Sema cue that, through spatially restricted expression of the receptor, signals in a ventricular chamber-specific manner to establish a distinct border between atrial and ventricular chambers that is important for functional development of the heart.

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Section: Discussionmentioning

confidence: 99%

Semaphorin3f as an intrinsic regulator of chamber-specific heart development

Halabi

Cechmanek

Hehr

et al. 2021

Preprint

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“…They confirmed the previously identified pattern of differentiation of FHF and SHF CPs, and through ligand–receptor analysis, the authors suggest the Mif – Cxcr2 pair as a possible mediator of the SHF CPs chemotaxis guided by CMs, which is a result that was confirmed by pharmacological inhibition and genetic knockouts of both Cxcr2/Cxcr4 . Similarly, lineage tracing combined with Smart-seq2 has been used to analyze the arterial specification in the sinus venosus [ 31 ] and epicardial development in zebrafish [ 32 ].…”

Section: Cardiac Scrnaseq During Embryonic and Postnatal Developmementioning

confidence: 99%

Ex uno, plures–From One Tissue to Many Cells: A Review of Single-Cell Transcriptomics in Cardiovascular Biology

Forte

McLellan

Skelly

et al. 2021

IJMS

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Recent technological advances have revolutionized the study of tissue biology and garnered a greater appreciation for tissue complexity. In order to understand cardiac development, heart tissue homeostasis, and the effects of stress and injury on the cardiovascular system, it is essential to characterize the heart at high cellular resolution. Single-cell profiling provides a more precise definition of tissue composition, cell differentiation trajectories, and intercellular communication, compared to classical bulk approaches. Here, we aim to review how recent single-cell multi-omic studies have changed our understanding of cell dynamics during cardiac development, and in the healthy and diseased adult myocardium.

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“…84,85 Difficulties in assessing whether epiEMT is complete or if epicardial cells-in vitro or in vivo-exist in one of several transitory states at any given time may contribute to perceived heterogeneity in epicardial gene expression and function. [85][86][87][88] The…”

Section: Epicardium: Native Friend or Foe In Cardiac Injury?mentioning

confidence: 99%

“…The EMT process represents a spectrum with multiple E‐to‐M states—both in development and injury 83 —which also allows for collective epicardial cell migration by leader cells with quasi‐mesenchymal phenotype 84,85 . Difficulties in assessing whether epiEMT is complete or if epicardial cells—in vitro or in vivo — exist in one of several transitory states at any given time may contribute to perceived heterogeneity in epicardial gene expression and function 85‐88 . The use of common epicardial markers similarly adds to this distraction, as they alone cannot distinguish epicardial cells from their transitory and differentiated progeny, as noted above.…”

Section: Recapturing Embryonic Potentialmentioning

confidence: 99%

Recapturing embryonic potential in the adult epicardium: Prospects for cardiac repair

Redpath

Smart

2020

Stem Cells Translational Medicine

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Research into potential targets for cardiac repair encompasses recognition of tissue-resident cells with intrinsic regenerative properties. The adult vertebrate heart is covered by mesothelium, named the epicardium, which becomes active in response to injury and contributes to repair, albeit suboptimally. Motivation to manipulate the epicardium for treatment of myocardial infarction is deeply rooted in its central role in cardiac formation and vasculogenesis during development. Moreover, the epicardium is vital to cardiac muscle regeneration in lower vertebrate and neonatal mammalian-injured hearts. In this review, we discuss our current understanding of the biology of the mammalian epicardium in development and injury. Considering present challenges in the field, we further contemplate prospects for reinstating full embryonic potential in the adult epicardium to facilitate cardiac regeneration.

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Functional Heterogeneity within the Developing Zebrafish Epicardium

Cited by 55 publications

References 90 publications

Semaphorin3f as an intrinsic regulator of chamber-specific heart development

Semaphorin3f as an intrinsic regulator of chamber-specific heart development

Ex uno, plures–From One Tissue to Many Cells: A Review of Single-Cell Transcriptomics in Cardiovascular Biology

Recapturing embryonic potential in the adult epicardium: Prospects for cardiac repair

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