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1. Lhx3/4 initiates a cardiopharyngeal-specific transcriptional program in response to widespread FGF signaling

   https://doi.org/10.1371/journal.pbio.3002169  

   Pickett, C. J.; Gruner, Hannah N.; Davidson, Bradley (January 2024, PLOS Biology)

   Kicheva, Anna Kostadinova (Ed.)

   Individual signaling pathways, such as fibroblast growth factors (FGFs), can regulate a plethora of inductive events. According to current paradigms, signal-dependent transcription factors (TFs), such as FGF/MapK-activated Ets family factors, partner with lineage-determining factors to achieve regulatory specificity. However, many aspects of this model have not been rigorously investigated. One key question relates to whether lineage-determining factors dictate lineage-specific responses to inductive signals or facilitate these responses in collaboration with other inputs. We utilize the chordate modelCiona robustato investigate mechanisms generating lineage-specific induction. Previous studies inC.robustahave shown that cardiopharyngeal progenitor cells are specified through the combined activity of FGF-activatedEts1/2.band an inferred ATTA-binding transcriptional cofactor. Here, we show that the homeobox TFLhx3/4serves as the lineage-determining TF that dictates cardiopharyngeal-specific transcription in response to pleiotropic FGF signaling. Targeted knockdown ofLhx3/4leads to loss of cardiopharyngeal gene expression. Strikingly, ectopic expression ofLhx3/4in a neuroectodermal lineage subject to FGF-dependent specification leads to ectopic cardiopharyngeal gene expression in this lineage. Furthermore, ectopicLhx3/4expression disrupts neural plate morphogenesis, generating aberrant cell behaviors associated with execution of incompatible morphogenetic programs. Based on these findings, we propose that combinatorial regulation by signal-dependent and lineage-determinant factors represents a generalizable, previously uncategorized regulatory subcircuit we term “cofactor-dependent induction.” Integration of this subcircuit into theoretical models will facilitate accurate predictions regarding the impact of gene regulatory network rewiring on evolutionary diversification and disease ontogeny. 

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2. A multiscale model via single-cell transcriptomics reveals robust patterning mechanisms during early mammalian embryo development

   https://doi.org/10.1371/journal.pcbi.1008571  

   Cang, Zixuan; Wang, Yangyang; Wang, Qixuan; Cho, Ken W.; Holmes, William; Nie, Qing (March 2021, PLOS Computational Biology)

   Umulis, David (Ed.)

   During early mammalian embryo development, a small number of cells make robust fate decisions at particular spatial locations in a tight time window to form inner cell mass (ICM), and later epiblast (Epi) and primitive endoderm (PE). While recent single-cell transcriptomics data allows scrutinization of heterogeneity of individual cells, consistent spatial and temporal mechanisms the early embryo utilize to robustly form the Epi/PE layers from ICM remain elusive. Here we build a multiscale three-dimensional model for mammalian embryo to recapitulate the observed patterning process from zygote to late blastocyst. By integrating the spatiotemporal information reconstructed from multiple single-cell transcriptomic datasets, the data-informed modeling analysis suggests two major processes critical to the formation of Epi/PE layers: a selective cell-cell adhesion mechanism (via EphA4/EphrinB2) for fate-location coordination and a temporal attenuation mechanism of cell signaling (via Fgf). Spatial imaging data and distinct subsets of single-cell gene expression data are then used to validate the predictions. Together, our study provides a multiscale framework that incorporates single-cell gene expression datasets to analyze gene regulations, cell-cell communications, and physical interactions among cells in complex geometries at single-cell resolution, with direct application to late-stage development of embryogenesis. 

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3. Accurate and efficient cell lineage tree inference from noisy single cell data: the maximum likelihood perfect phylogeny approach

   https://doi.org/10.1093/bioinformatics/btz676  

   Wu, Yufeng (August 2019, Bioinformatics)

   Schwartz, Russell (Ed.)

   Abstract Motivation Cells in an organism share a common evolutionary history, called cell lineage tree. Cell lineage tree can be inferred from single cell genotypes at genomic variation sites. Cell lineage tree inference from noisy single cell data is a challenging computational problem. Most existing methods for cell lineage tree inference assume uniform uncertainty in genotypes. A key missing aspect is that real single cell data usually has non-uniform uncertainty in individual genotypes. Moreover, existing methods are often sampling based and can be very slow for large data. Results In this article, we propose a new method called ScisTree, which infers cell lineage tree and calls genotypes from noisy single cell genotype data. Different from most existing approaches, ScisTree works with genotype probabilities of individual genotypes (which can be computed by existing single cell genotype callers). ScisTree assumes the infinite sites model. Given uncertain genotypes with individualized probabilities, ScisTree implements a fast heuristic for inferring cell lineage tree and calling the genotypes that allow the so-called perfect phylogeny and maximize the likelihood of the genotypes. Through simulation, we show that ScisTree performs well on the accuracy of inferred trees, and is much more efficient than existing methods. The efficiency of ScisTree enables new applications including imputation of the so-called doublets. Availability and implementation The program ScisTree is available for download at: https://github.com/yufengwudcs/ScisTree. Supplementary information Supplementary data are available at Bioinformatics online. 

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4. Investigating the Intracluster Medium Viscosity Using the Tails of GASP Jellyfish Galaxies

   https://doi.org/10.3847/1538-4357/ad919b  

   Ignesti, Alessandro; Brunetti, Gianfranco; Gullieuszik, Marco; Akerman, Nina; Marasco, Antonino; Poggianti, Bianca M; Li, Yuan; Vulcani, Benedetta; Gitti, Myriam; Moretti, Alessia; et al (December 2024, The Astrophysical Journal)

   Abstract The microphysics of the intracluster medium (ICM) in galaxy clusters is still poorly understood. Observational evidence suggests that the effective viscosity is suppressed by plasma instabilities that reduce the mean free path of particles. Measuring the effective viscosity of the ICM is crucial to understanding the processes that govern its physics on small scales. The trails of ionized interstellar medium left behind by the so-called jellyfish galaxies can trace the turbulent motions of the surrounding ICM and constrain its local viscosity. We present the results of a systematic analysis of the velocity structure function (VSF) of the Hαline for ten galaxies from the GASP sample. The VSFs show a sublinear power-law scaling below 10 kpc that may result from turbulent cascading and extends to 1 kpc, which is below the supposed ICM dissipation scales of tens of kpc expected in a fluid described by Coulomb collisions. Our result constrains the local ICM viscosity to be 0.3%–25% of the expected Spitzer value. Our findings demonstrate that either the ICM particles have a smaller mean free path than expected in a regime defined by Coulomb collisions or that we are probing effects due to collisionless physics in the ICM turbulence. 

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5. Molecular mechanisms of tubulogenesis revealed in the sea star hydro-vascular organ

   https://doi.org/10.1038/s41467-023-37947-2  

   Perillo, Margherita; Swartz, S Zachary; Pieplow, Cosmo; Wessel, Gary M (December 2023, Nature Communications)

   Abstract A fundamental goal in the organogenesis field is to understand how cells organize into tubular shapes. Toward this aim, we have established the hydro-vascular organ in the sea starPatiria miniataas a model for tubulogenesis. In this animal, bilateral tubes grow out from the tip of the developing gut, and precisely extend to specific sites in the larva. This growth involves cell migration coupled with mitosis in distinct zones. Cell proliferation requires FGF signaling, whereas the three-dimensional orientation of the organ depends on Wnt signaling. Specification and maintenance of tube cell fate requires Delta/Notch signaling. Moreover, we identify target genes of the FGF pathway that contribute to tube morphology, revealing molecular mechanisms for tube outgrowth. Finally, we report that FGF activates the Six1/2 transcription factor, which serves as an evolutionarily ancient regulator of branching morphogenesis. This study uncovers distinct mechanisms of tubulogenesis in vivo and we propose that cellular dynamics in the sea star hydro-vascular organ represents a key comparison for understanding the evolution of vertebrate organs. 

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