Understanding how changes in developmental gene expression alter morphogenesis is a fundamental problem in development and evolution. A promising approach to address this problem is to compare the developmental transcriptomes between related species. The echinoderm phylum consists of several model species that have significantly contributed to the understanding of gene regulation and evolution. Particularly, the regulatory networks of the sea star,
The developmental gene regulatory networks (dGRNs) of two sea urchin species,
- Award ID(s):
- 1929934
- NSF-PAR ID:
- 10423150
- Publisher / Repository:
- Springer Science + Business Media
- Date Published:
- Journal Name:
- EvoDevo
- Volume:
- 14
- Issue:
- 1
- ISSN:
- 2041-9139
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Patiria miniata (P .miniata ), have been extensively studied, however developmental transcriptomes for this species were lacking. Here we generated developmental transcriptomes ofP .miniata and compared these with those of two sea urchins species. We demonstrate that the conservation of gene expression depends on gene function, cell type and evolutionary distance. With increasing evolutionary distance the interspecies correlations in gene expression decreases. The reduction is more severe in the correlations between morphologically equivalent stages (diagonal elements) than in the correlation between morphologically distinct stages (off-diagonal elements). This could reflect a decrease in the morphological constraints compared to other constraints that shape gene expression at large evolutionary divergence. Within this trend, the interspecies correlations of developmental control genes maintain their diagonality at large evolutionary distance, and peak at the onset of gastrulation, supporting the hourglass model of phylotypic stage conservation. -
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ABSTRACT Using scRNA-seq coupled with computational approaches, we studied transcriptional changes in cell states of sea urchin embryos during development to the larval stage. Eighteen closely spaced time points were taken during the first 24 h of development of Lytechinus variegatus (Lv). Developmental trajectories were constructed using Waddington-OT, a computational approach to ‘stitch’ together developmental time points. Skeletogenic and primordial germ cell trajectories diverged early in cleavage. Ectodermal progenitors were distinct from other lineages by the 6th cleavage, although a small percentage of ectoderm cells briefly co-expressed endoderm markers that indicated an early ecto-endoderm cell state, likely in cells originating from the equatorial region of the egg. Endomesoderm cells also originated at the 6th cleavage and this state persisted for more than two cleavages, then diverged into distinct endoderm and mesoderm fates asynchronously, with some cells retaining an intermediate specification status until gastrulation. Seventy-nine out of 80 genes (99%) examined, and included in published developmental gene regulatory networks (dGRNs), are present in the Lv-scRNA-seq dataset and are expressed in the correct lineages in which the dGRN circuits operate.
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Embryonic development is arguably the most complex process an organism undergoes during its lifetime, and understanding this complexity is best approached with a systems-level perspective. The sea urchin has become a highly valuable model organism for understanding developmental specification, morphogenesis, and evolution. As a non-chordate deuterostome, the sea urchin occupies an important evolutionary niche between protostomes and vertebrates. Lytechinus variegatus (Lv) is an Atlantic species that has been well studied, and which has provided important insights into signal transduction, patterning, and morphogenetic changes during embryonic and larval development. The Pacific species, Strongylocentrotus purpuratus (Sp), is another well-studied sea urchin, particularly for gene regulatory networks (GRNs) and cis-regulatory analyses. A well-annotated genome and transcriptome for Sp are available, but similar resources have not been developed for Lv. Here, we provide an analysis of the Lv transcriptome at 11 timepoints during embryonic and larval development. Temporal analysis suggests that the gene regulatory networks that underlie specification are well-conserved among sea urchin species. We show that the major transitions in variation of embryonic transcription divide the developmental time series into four distinct, temporally sequential phases. Our work shows that sea urchin development occurs via sequential intervals of relatively stable gene expression states that are punctuated by abrupt transitions.more » « less
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Newman, Stuart A (Ed.)Cellular differentiation during hematopoiesis is guided by gene regulatory networks (GRNs) comprising transcription factors (TFs) and the effectors of cytokine signaling. Based largely on analyses conducted at steady state, these GRNs are thought to be organized as a hierarchy of bistable switches, with antagonism between Gata1 and PU.1 driving red- and white-blood cell differentiation. Here, we utilize transient gene expression patterns to infer the genetic architecture—the type and strength of regulatory interconnections—and dynamics of a twelve-gene GRN including key TFs and cytokine receptors. We trained gene circuits, dynamical models that learn genetic architecture, on high temporal-resolution gene-expression data from the differentiation of an inducible cell line into erythrocytes and neutrophils. The model is able to predict the consequences of gene knockout, knockdown, and overexpression experiments and the inferred interconnections are largely consistent with prior empirical evidence. The inferred genetic architecture is densely interconnected rather than hierarchical, featuring extensive cross-antagonism between genes from alternative lineages and positive feedback from cytokine receptors. The analysis of the dynamics of gene regulation in the model reveals that PU.1 is one of the last genes to be upregulated in neutrophil conditions and that the upregulation of PU.1 and other neutrophil genes is driven by Cebpa and Gfi1 instead. This model inference is confirmed in an independent single-cell RNA-Seq dataset from mouse bone marrow in which Cebpa and Gfi1 expression precedes the neutrophil-specific upregulation of PU.1 during differentiation. These results demonstrate that full PU.1 upregulation during neutrophil development involves regulatory influences extrinsic to the Gata1-PU.1 bistable switch. Furthermore, although there is extensive cross-antagonism between erythroid and neutrophil genes, it does not have a hierarchical structure. More generally, we show that the combination of high-resolution time series data and data-driven dynamical modeling can uncover the dynamics and causality of developmental events that might otherwise be obscured.more » « less
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Summary Cell differentiation is driven by changes in the activity of transcription factors (
TF s) and subsequent alterations in transcription. To study this process, differences inTF binding between cell types can be deduced by probing chromatin accessibility. We used cell type‐specific nuclear purification followed by the assay for transposase‐accessible chromatin (ATAC ‐seq) to delineate differences in chromatin accessibility andTF regulatory networks between stem cells of the shoot apical meristem (SAM ) and differentiated leaf mesophyll cells inArabidopsis thaliana . Chromatin accessibility profiles ofSAM stem cells and leaf mesophyll cells were very similar at a qualitative level, yet thousands of regions having quantitatively different chromatin accessibility were also identified. Analysis of the genomic regions preferentially accessible in each cell type identified hundreds of overrepresentedTF ‐binding motifs, highlighting sets ofTF s that are probably important for each cell type. Within these sets, we found evidence for extensive co‐regulation of target genes by multipleTF s that are preferentially expressed in each cell type. Interestingly, theTF s within each of these cell type‐enriched sets also showed evidence of extensively co‐regulating each other. We further found that preferentially accessible chromatin regions in mesophyll cells tended to also be substantially accessible in the stem cells, whereas the converse was not true. This observation suggests that the generally higher accessibility of regulatory elements in stem cells might contribute to their developmental plasticity. This work demonstrates the utility of cell type‐specific chromatin accessibility profiling for the rapid development of testable models of regulatory control differences between cell types.
