Assessing evolutionary and developmental transcriptome dynamics in homologous cell types

Feregrino, Christian; Tschopp, Patrick

doi:10.1101/2021.02.09.430383

Cited by 4 publications

(2 citation statements)

References 82 publications

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“…Particularly, as our data only captures the earliest stages of limb initiation, integrative analysis with later stages of limb patterning (Feregrino et al, 2019;Feregrino and Tschopp, 2021) provides an opportunity to reconstruct the full cellular and developmental events underlying forelimb initiation, patterning and development. Furthermore, while we shed light on the genetic hierarchy that is active during LPM specification, the gene regulatory networks accompanying these are unknown.…”

Section: Discussionmentioning

confidence: 99%

Cell lineage specification during development of the anterior lateral plate mesoderm and forelimb field

Newton

Williams

Major

et al. 2022

Preprint

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The lateral plate mesoderm (LPM) is a transient embryonic tissue that gives rise to a diverse range of mature cell types, including the cardiovascular system, the urogenital system, endoskeleton of the limbs, and mesenchyme of the gut. While the genetic processes that drive development of these tissues are well defined, the early cell fate choices underlying LPM development and specification are poorly understood. In this study, we utilize single-cell transcriptomics to define cell lineage specification during development of the anterior LPM and the forelimb field in the chicken embryo. We identify the molecular pathways directing differentiation of the aLPM towards a somatic or splanchnic cell fate, and subsequent emergence of the forelimb mesenchyme. We establish the first transcriptional atlas of progenitor, transitional and mature cell types throughout the early forelimb field and uncover the global signalling pathways which are active during LPM differentiation and forelimb initiation. Specification of the somatic and splanchnic LPM from undifferentiated mesoderm utilizes distinct signalling pathways and involves shared repression of early mesodermal markers, followed by activation of lineage-specific gene modules. We identify rapid activation of the transcription factor TWIST1 in the somatic LPM preceding activation of known limb initiation genes, such as TBX5, which plays a likely role in epithelial-to-mesenchyme transition of the limb bud mesenchyme. Furthermore, development of the somatic LPM and limb is dependent on ectodermal BMP signalling, where BMP antagonism reduces expression of key somatic LPM and limb genes to inhibit formation of the limb bud mesenchyme. Together, these findings provide new insights into molecular mechanisms that drive fate cell choices during specification of the aLPM and forelimb initiation.

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Section: Discussionmentioning

confidence: 99%

Cell lineage specification during development of the anterior lateral plate mesoderm and forelimb field

Newton

Williams

Major

et al. 2022

Preprint

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“…Theoretical concepts underlying the evolution of cell type diversity and the process of evolution in different cell types within a tissue are well-developed (reviewed in Arendt et al 2016; Musser and Wagner 2015). Single-cell data in evolutionary contexts have generally been applied to distantly related taxa (Tosches et al 2018; Hodge et al 2019; Liang et al 2018), typically focusing on cell type diversity (Sebé-Pedrós et al 2018; La Manno et al 2016; Colquitt et al 2021; Feregrino and Tschopp 2021; J. Wang et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Single-nucleus transcriptomes reveal functional and evolutionary properties of cell types in the Drosophila accessory gland

2021

Preprint

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Many traits responsible for male reproduction evolve quickly, including gene expression phenotypes in germline and somatic male reproductive tissues. Rapid male evolution in polyandrous species is thought to be driven by competition among males for fertilizations and conflicts between male and female fitness interests that manifest in post-copulatory phenotypes. In Drosophila, seminal fluid proteins secreted by three major cell types of the male accessory gland and ejaculatory duct are required for female sperm storage and use, and influence female post-copulatory traits. Recent work has shown that these cell types have overlapping but distinct effects on female post-copulatory biology, yet relatively little is known about their evolutionary properties. Here we use single-nucleus RNA-Seq of the accessory gland and ejaculatory duct from Drosophila melanogaster and two closely related species to comprehensively describe the cell diversity of these tissues and their transcriptome evolution for the first time. We find that seminal fluid transcripts are strongly partitioned across the major cell types, and expression of many other genes additionally define each cell type. We also report previously undocumented diversity in main cells. Transcriptome divergence was found to be heterogeneous across cell types and lineages, revealing a complex evolutionary process. Furthermore, protein adaptation varied across cell types, with potential consequences for our understanding of selection on male post-copulatory traits.

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Inter-gastruloid heterogeneity revealed by single cell transcriptomics time course: implications for organoid based perturbation studies

Rosen

Stapel

Argelaguet³

et al. 2022

Preprint

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Recent advances in organoid and genome editing technologies are allowing for perturbation experiments at an unprecedented scale. However, before doing such experiments it is important to understand the gene expression profile in each of the organoid's cells, as well as how much heterogeneity there is between individual organoids. Here we characterise an organoid model of mouse gastrulation called gastruloids using single cell RNA-sequencing of individual organoids at half-day intervals between day 3 and day 5 of differentiation (roughly corresponding to E6.5-E8.75 in vivo). Our study reveals multiple differentiation trajectories that have hitherto not been characterised in gastruloids. Intriguingly, we observe that individual gastruloids displayed a strong bias towards producing either mesodermal (largely somitic) or ectodermal (specifically neural) cell types. This bifurcation is already seen at the earliest sampled time point, and is characterised by increased activity of WNT-associated pathways in mesodermally-biased gastruloids as compared to neurally-biased gastruloids. Notably, at day 5, mesodermal gastruloids show an increase in the proportion of neural cells, while neural gastruloids do not produce notably more mesodermal cells. This is in line with previous studies on how the balance between these cell types is regulated. We demonstrate using in silico simulations that without proper understanding of the inter-organoid heterogeneity, perturbation experiments have either very high false positive or negative rates, depending on the statistical model used. Thus in future studies, modelling of inter-organoid heterogeneity will be crucial when designing organoid-based perturbation studies.

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Assessing evolutionary and developmental transcriptome dynamics in homologous cell types

Cited by 4 publications

References 82 publications

Cell lineage specification during development of the anterior lateral plate mesoderm and forelimb field

Cell lineage specification during development of the anterior lateral plate mesoderm and forelimb field

Single-nucleus transcriptomes reveal functional and evolutionary properties of cell types in the Drosophila accessory gland

Inter-gastruloid heterogeneity revealed by single cell transcriptomics time course: implications for organoid based perturbation studies

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