scholarly journals Developmental single-cell transcriptomics in the Lytechinus variegatus sea urchin embryo

Development ◽  
2021 ◽  
Author(s):  
Abdull J. Massri ◽  
Laura Greenstreet ◽  
Anton Afanassiev ◽  
Alejandro Berrio ◽  
Gregory A. Wray ◽  
...  
Keyword(s):  
Sea Urchin ◽  
Regulatory Networks ◽  
Developmental Trajectories ◽  
Primordial Germ Cell ◽  
Equatorial Region ◽  
Lytechinus Variegatus ◽  
Sea Urchin Embryo ◽  
Transcriptional Changes ◽  
Gene Regulatory ◽  
Cell Trajectories

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 hours of development of Lytechinus variegatus (Lv). Developmental trajectories were constructed using Waddington-OT, a computational approach to "stitch" together developmental timepoints. Skeletogenic and primordial germ cell trajectories diverged early in cleavage. Ectodermal progenitors were distinct from other lineages by sixth cleavage, though a small percentage of ectoderm cells briefly co-expressed endoderm markers indicating an early ecto-endoderm cell state, likely in cells originating from the equatorial region of the egg. Endomesoderm cells originated at 6th cleavage also 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. 79 of 80 genes (99%) examined, and included in published developmental gene regulatory networks (dGRNs), are present in the Lv-scRNA-seq dataset, and expressed in the correct lineages in which the dGRN circuits operate.

scholarly journals Developmental Single-cell transcriptomics in the Lytechinus variegatus Sea Urchin Embryo

2020 ◽  
Author(s):  
Abdull J. Massri ◽  
Laura Greenstreet ◽  
Anton Afanassiev ◽  
Alejandro Berrio Escobar ◽  
Gregory M. Wray ◽  
...  
Keyword(s):  
Gene Regulatory Network ◽  
Sea Urchin ◽  
Regulatory Network ◽  
Developmental Trajectories ◽  
Lytechinus Variegatus ◽  
Time Points ◽  
Sea Urchin Embryo ◽  
The Face ◽  
Gene Regulatory ◽  
Changes Over Time

AbstractHere we employed scRNA-seq coupled with computational approaches to examine molecular changes in cells during specification and differentiation. We examined the first 24 hours of development of the sea urchin Lytechinus variegatus (Lv) with 18 time points during which the embryo develops to the larval stage. Using Waddington-OT, the time points were computationally “stitched” together to calculate developmental trajectories. Skeletogenic cells displayed the expected immediate early divergence while other lineages diverged asynchronously, with many cells retaining an intermediate specification status until late in gastrulation. The Lv-scRNA-seq dataset was compared to the developmental Gene Regulatory Network (dGRN) model of specification in Strongylocentrotus purpuratus (Sp). 79 of 80 genes (98%) in that dGRN are present in the Lv-scRNA-seq dataset, and expressed in the correct lineages in which the dGRN circuits operate. Surprisingly, however, many heterochronies in timing of first expression of dGRN genes have evolved between the two species. Replotting the two dGRNs with precise attention to time of expression revealed a number of feedback inputs that likely buffer the dGRNs, allowing them to maintain function in the face of accumulating heterochronies.Summary statementThe early development of the sea urchin embryo was followed using scRNA-seq plus computational methods to trace lineage diversifications. These were matched to gene regulatory network changes over time.

scholarly journals The Developmental Transcriptome for Lytechinus variegatus Exhibits Temporally Punctuated Gene Expression Changes

2019 ◽  
Author(s):  
John D. Hogan ◽  
Jessica L. Keenan ◽  
Lingqi Luo ◽  
Dakota Y. Hawkins ◽  
Jonas Ibn-Salem ◽  
...  
Keyword(s):  
Gene Expression ◽  
Larval Development ◽  
Sea Urchin ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Lytechinus Variegatus ◽  
Stable Gene ◽  
Major Transitions ◽  
Gene Regulatory ◽  
Embryonic And Larval Development

AbstractEmbryonic 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. The data indicate 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.

scholarly journals Spdeadringer, a sea urchin embryo gene required separately in skeletogenic and oral ectoderm gene regulatory networks

2003 ◽  
Vol 261 (1) ◽  
pp. 55-81 ◽  
Author(s):  
Gabriele Amore ◽  
Robert G Yavrouian ◽  
Kevin J Peterson ◽  
Andrew Ransick ◽  
David R McClay ◽  
...  
Keyword(s):  
Sea Urchin ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Sea Urchin Embryo ◽  
Oral Ectoderm ◽  
Gene Regulatory

scholarly journals Deployment of a retinal determination gene network drives directed cell migration in the sea urchin embryo

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Megan L Martik ◽  
David R McClay
Keyword(s):  
Sea Urchin ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Regulatory Control ◽  
Directed Cell Migration ◽  
Multipotent Progenitors ◽  
Retinal Determination ◽  
Sea Urchin Embryo ◽  
Gene Regulatory ◽  
Retinal Determination Gene Network

Gene regulatory networks (GRNs) provide a systems-level orchestration of an organism's genome encoded anatomy. As biological networks are revealed, they continue to answer many questions including knowledge of how GRNs control morphogenetic movements and how GRNs evolve. The migration of the small micromeres to the coelomic pouches in the sea urchin embryo provides an exceptional model for understanding the genomic regulatory control of morphogenesis. An assay using the robust homing potential of these cells reveals a ‘coherent feed-forward’ transcriptional subcircuit composed of Pax6, Six3, Six1/2, Eya, and Dach1 that is responsible for the directed homing mechanism of these multipotent progenitors. The linkages of that circuit are strikingly similar to a circuit involved in retinal specification in Drosophila suggesting that systems-level tasks can be highly conserved even though the tasks drive unrelated processes in different animals.

scholarly journals The tolerance to hypoxia is defined by a time-sensitive response of the gene regulatory network in sea urchin embryos

Development ◽  
2021 ◽  
pp. dev.195859
Author(s):  
Majed Layous ◽  
Lama Khalaily ◽  
Tsvia Gildor ◽  
Smadar Ben-Tabou de-Leon
Keyword(s):  
Early Development ◽  
Sea Urchin ◽  
Regulatory Networks ◽  
Normal Development ◽  
Axis Formation ◽  
Oxygen Level ◽  
Sea Urchin Embryo ◽  
Tolerance To Hypoxia ◽  
Vegf Pathway ◽  
Gene Regulatory

Deoxygenation, the reduction of oxygen level in the oceans induced by global warming and anthropogenic disturbances, is a major threat to marine life. This change in oxygen level could be especially harmful to marine embryos that utilize endogenous hypoxia and redox gradients as morphogens during normal development. Here we show that the tolerance to hypoxic conditions changes between different developmental stages of the sea urchin embryo, possibly due to the structure of the gene regulatory networks (GRNs). We demonstrate that during normal development, bone morphogenetic protein (BMP) pathway restricts the activity of the vascular endothelial growth factor (VEGF) pathway to two lateral domains and by that controls proper skeletal patterning. Hypoxia applied during early development strongly perturbs the activity of Nodal and BMP pathways that affect VEGF pathway, dorsal-ventral (DV) and skeletogenic patterning. These pathways are largely unaffected by hypoxia applied after DV-axis formation. We propose that the use of redox and hypoxia as morphogens makes the sea urchin embryo highly sensitive to environmental hypoxia during early development, but the GRN structure provides higher tolerance to hypoxia at later stages.

scholarly journals Identification of drugs for leukaemia differentiation therapy by network pharmacology

2019 ◽  
Author(s):  
Eleni G Christodoulou ◽  
Lin Ming Lee ◽  
Kian Leong Lee ◽  
Tsz Kan Fung ◽  
Eric So ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cellular Reprogramming ◽  
Network Pharmacology ◽  
Differentiation Therapy ◽  
Disease States ◽  
Small Molecule Drugs ◽  
Transcriptional Changes ◽  
Gene Regulatory ◽  
Computational Platform

AbstractAcute leukaemias differ from their normal haematopoietic counterparts in their inability to differentiate. This phenomenon is thought to be the result of aberrant cellular reprogramming involving transcription factors (TFs). Here we leveraged on Mogrify, a network-based algorithm, to identify TFs and their gene regulatory networks that drive differentiation of the acute promyelocytic leukaemia (APL) cell line NB4 in response to ATRA (all-transretinoic acid). We further integrated the detected TF regulatory networks with the Connectivity Map (CMAP) repository and recovered small molecule drugs which induce similar transcriptional changes. Our method outperformed standard approaches, retrieving ATRA as the top hit. Of the other drug hits, dimaprit and mebendazole enhanced ATRA-mediated differentiation in both parental NB4 and ATRA-resistant NB4-MR2 cells. Thus, we provide proof-of-principle of our network-based computational platform for drug discovery and repositioning in leukaemia differentiation therapy, which can be extended to other dysregulated disease states.

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