A single cell transcriptional roadmap for cardiopharyngeal fate diversification

AbstractIn vertebrates, multipotent progenitors located in the pharyngeal mesoderm form cardiomyocytes and branchiomeric head muscles, but the dynamic gene expression programs and mechanisms underlying cardiopharyngeal multipotency and heart vs. head muscle fate choices remain elusive. Here, we used single cell genomics in the simple chordate model Ciona, to reconstruct developmental trajectories forming first and second heart lineages, and pharyngeal muscle precursors, and characterize the molecular underpinnings of cardiopharyngeal fate choices. We show that FGF-MAPK signaling maintains multipotency and promotes the pharyngeal muscle fate, whereas signal termination permits the deployment of a pan-cardiac program, shared by the first and second lineages, to define heart identity. In the second heart lineage, a Tbx1/10-Dach pathway actively suppresses the first heart lineage program, conditioning later cell diversity in the beating heart. Finally, cross-species comparisons between Ciona and the mouse evoke the deep evolutionary origins of cardiopharyngeal networks in chordates.

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An FGF-driven feed-forward circuit patterns the cardiopharyngeal mesoderm in space and time

10.1101/138701 ◽

2017 ◽

Cited By ~ 1

Author(s):

Florian Razy-Krajka ◽

Basile Gravez ◽

Nicole Kaplan ◽

Claudia Racioppi ◽

Wei Wang ◽

...

Keyword(s):

Cell Types ◽

Mapk Signaling ◽

Full Potential ◽

Pharyngeal Muscle ◽

Feed Forward ◽

Second Heart Field ◽

Cell Divisions ◽

Multipotent Progenitors ◽

Heart Field ◽

Head Muscles

AbstractIn embryos, multipotent progenitors divide to produce distinct progeny and express their full potential. In vertebrates, multipotent cardiopharyngeal progenitors produce second-heart-field-derived cardiomyocytes, and branchiomeric skeletal head muscles. However, the mechanisms underlying these early fate choices remain largely elusive. The tunicate Ciona emerged as an attractive model to study early cardiopharyngeal development at high resolution: through two asymmetric and oriented divisions, defined cardiopharyngeal progenitors produce distinct first and second heart precursors, and pharyngeal muscle (aka atrial siphon muscle, ASM) precursors. Here, we demonstrate that differential FGF-MAPK signaling distinguishes between heart and ASM precursors. We characterize a feed-forward circuit that promotes the successive activations of essential ASM determinants, Hand-related, Tbx1/10 and Ebf. Finally, we show that coupling FGF-MAPK restriction and cardiopharyngeal network deployment with cell divisions defines the timing of gene expression and permits the emergence of diverse cell types from multipotent progenitors.

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An FGF-driven feed-forward circuit patterns the cardiopharyngeal mesoderm in space and time

eLife ◽

10.7554/elife.29656 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 12

Author(s):

Florian Razy-Krajka ◽

Basile Gravez ◽

Nicole Kaplan ◽

Claudia Racioppi ◽

Wei Wang ◽

...

Keyword(s):

Cell Types ◽

Mapk Signaling ◽

Full Potential ◽

Pharyngeal Muscle ◽

Feed Forward ◽

Second Heart Field ◽

Cell Divisions ◽

Multipotent Progenitors ◽

Heart Field ◽

Head Muscles

In embryos, multipotent progenitors divide to produce distinct progeny and express their full potential. In vertebrates, multipotent cardiopharyngeal progenitors produce second-heart-field-derived cardiomyocytes, and branchiomeric skeletal head muscles. However, the mechanisms underlying these early fate choices remain largely elusive. The tunicate Ciona emerged as an attractive model to study early cardiopharyngeal development at high resolution: through two asymmetric and oriented divisions, defined cardiopharyngeal progenitors produce distinct first and second heart precursors, and pharyngeal muscle (aka atrial siphon muscle, ASM) precursors. Here, we demonstrate that differential FGF-MAPK signaling distinguishes between heart and ASM precursors. We characterize a feed-forward circuit that promotes the successive activations of essential ASM determinants, Hand-related, Tbx1/10 and Ebf. Finally, we show that coupling FGF-MAPK restriction and cardiopharyngeal network deployment with cell divisions defines the timing of gene expression and permits the emergence of diverse cell types from multipotent progenitors.

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Rnf149-related is an FGF/MAPK-independent regulator of pharyngeal muscle fate specification

10.1101/2022.01.07.475354 ◽

2022 ◽

Author(s):

Burcu Vitrinel ◽

Christine Vogel ◽

Lionel Christiaen

Keyword(s):

Cell Fate ◽

Mapk Signaling ◽

Integrated Analysis ◽

Specific Gene ◽

Loss Of Function ◽

Pharyngeal Muscle ◽

Knock Out ◽

Fate Specification ◽

Multipotent Progenitors ◽

Pharyngeal Muscles

During embryonic development, cell fate specification gives rise to dedicated lineages that underlie tissue formation. In olfactores, which comprise tunicates and vertebrates, the cardiopharyngeal field is formed by multipotent progenitors to both cardiac and branchiomeric muscles. The ascidian Ciona is a powerful model to study the cardiopharyngeal fate specification with cellular resolution, as only 2 pairs of cardiopharyngeal multipotent progenitors give rise to the heart and to pharyngeal muscles (aka atrial siphon muscles, ASM). These progenitors are multilineage primed, in as much as they express a combination of early ASM- and heart-specific transcripts that become restricted to their corresponding precursors, following oriented asymmetric divisions. Here, we identify the primed gene Rnf149-related (Rnf149-r), which becomes restricted to the heart progenitors, but appears to regulate pharyngeal muscle fate specification in the cardiopharyngeal lineage. CRISPR/Cas9-mediated loss knock-out of Rnf149-r function impairs atrial siphon muscle morphogenesis, and down-regulates Tbx1/10 and Ebf, two key determinants of the pharyngeal muscle fate, while upregulating heart-specific gene expression. These phenotypes are reminiscent of loss of FGF-MAPK signaling in the cardiopharyngeal lineage, and integrated analysis of lineage-specific bulk RNA-seq profiling of loss-of-function perturbations identified a significant overlap between FGF-MAPK and Rnf149-r targets. However, functional interaction assays suggested the Rnf149-r does not directly modulate the activity of the FGF-MAPK-Ets1/2 pathway. Instead, we propose that Rnf149-r acts both in parallel to the FGF-MAPK signaling on shared targets, as well as on FGF-MAPK-independent targets through (a) separate pathway(s).

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Spatiotemporal Developmental Trajectories in the Arabidopsis Root Revealed Using High-Throughput Single Cell RNA Sequencing

SSRN Electronic Journal ◽

10.2139/ssrn.3300042 ◽

2018 ◽

Author(s):

Tom Denyer ◽

Xiaoli Ma ◽

Simon Klesen ◽

Emanuele Scacchi ◽

Kay Nieselt ◽

...

Keyword(s):

Single Cell ◽

Rna Sequencing ◽

High Throughput ◽

Developmental Trajectories ◽

Arabidopsis Root ◽

Single Cell Rna Sequencing

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Rejoinder for “Exponential-Family Embedding With Application to Cell Developmental Trajectories for Single-Cell RNA-Seq Data”

Journal of the American Statistical Association ◽

10.1080/01621459.2021.1892701 ◽

2021 ◽

Vol 116 (534) ◽

pp. 478-480

Author(s):

Kevin Z. Lin ◽

Jing Lei ◽

Kathryn Roeder

Keyword(s):

Single Cell ◽

Exponential Family ◽

Developmental Trajectories ◽

Rna Seq

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Discussion of “Exponential-Family Embedding With Application to Cell Developmental Trajectories for Single-Cell RNA-Seq Data”

Journal of the American Statistical Association ◽

10.1080/01621459.2021.1880919 ◽

2021 ◽

Vol 116 (534) ◽

pp. 475-477

Author(s):

Jian Hu ◽

Mingyao Li

Keyword(s):

Single Cell ◽

Exponential Family ◽

Developmental Trajectories ◽

Rna Seq

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Disentangling neural cell diversity using single-cell transcriptomics

Nature Neuroscience ◽

10.1038/nn.4366 ◽

2016 ◽

Vol 19 (9) ◽

pp. 1131-1141 ◽

Cited By ~ 189

Author(s):

Jean-Francois Poulin ◽

Bosiljka Tasic ◽

Jens Hjerling-Leffler ◽

Jeffrey M Trimarchi ◽

Rajeshwar Awatramani

Keyword(s):

Single Cell ◽

Neural Cell ◽

Cell Diversity

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Single-cell transcriptomic analysis identifies neocortical developmental differences between human and mouse

10.1101/2020.04.23.056390 ◽

2020 ◽

Author(s):

Ziheng Zhou ◽

Shuguang Wang ◽

Dengwei Zhang ◽

Xiaosen Jiang ◽

Jie Li ◽

...

Keyword(s):

Cerebral Cortex ◽

Single Cell ◽

Developmental Trajectories ◽

Expression Patterns ◽

Development Stage ◽

Inhibitory Neurons ◽

Projection Neurons ◽

Cerebral Cortex Development ◽

Excitatory Neurons ◽

Human And Mouse

AbstractBackgroundThe specification and differentiation of neocortical projection neurons is a complex process under precise molecular regulation; however, little is known about the similarities and differences in cerebral cortex development between human and mouse at single-cell resolution.ResultsHere, using single-cell RNA-seq (scRNA-seq) data we explore the divergence and conservation of human and mouse cerebral cortex development using 18,446 and 7,610 neocortical cells. Systematic cross-species comparison reveals that the overall transcriptome profile in human cerebral cortex is similar to that in mouse such as cell types and their markers genes. By single-cell trajectories analysis we find human and mouse excitatory neurons have different developmental trajectories of neocortical projection neurons, ligand-receptor interactions and gene expression patterns. Further analysis reveals a refinement of neuron differentiation that occurred in human but not in mouse, suggesting that excitatory neurons in human undergo refined transcriptional states in later development stage. By contrast, for glial cells and inhibitory neurons we detected conserved developmental trajectories in human and mouse.ConclusionsTaken together, our study integrates scRNA-seq data of cerebral cortex development in human and mouse, and uncovers distinct developing models in neocortical projection neurons. The earlier activation of cognition -related genes in human may explain the differences in behavior, learning or memory abilities between the two species.

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An analysis of the response to gut induction in the C. elegans embryo

Development ◽

10.1242/dev.121.4.1227 ◽

1995 ◽

Vol 121 (4) ◽

pp. 1227-1236 ◽

Cited By ~ 7

Author(s):

B. Goldstein

Keyword(s):

Body Wall ◽

Cell Lineage ◽

Muscle Cells ◽

The Other ◽

Cell Stage ◽

Pharyngeal Muscle ◽

Cell Cycles ◽

Sister Cell ◽

C Elegans ◽

Cell Diversity

Establishment of the gut founder cell (E) in C. elegans involves an interaction between the P2 and the EMS cell at the four cell stage. Here I show that the fate of only one daughter of EMS, the E cell, is affected by this induction. In the absence of the P2-EMS interaction, both E and its sister cell, MS, produce pharyngeal muscle cells and body wall muscle cells, much as MS normally does. By cell manipulations and inhibitor studies, I show first that EMS loses the competence to respond before it divides even once, but P2 presents an inducing signal for at least three cell cycles. Second, induction on one side of the EMS cell usually blocks the other side from responding to a second P2-derived signal. Third, microfilaments and microtubules may be required near the time of the interaction for subsequent gut differentiation. Lastly, cell manipulations in pie-1 mutant embryos, in which the P2 cell is transformed to an EMS-like fate and produces a gut cell lineage, revealed that gut fate is segregated to one of P2's daughters cell-autonomously. The results contrast with previous results from similar experiments on the response to other inductions, and suggest that this induction may generate cell diversity by a different mechanism.

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