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Lammers, N.

Publications and source records attributed to Lammers, N..

3 recordsLinked to original sources

Early immune cell development precedes gastrulation in annual killifish

During embryogenesis, cell types arise in a predictable order because developmental regulators act sequentially. But how evolutionary changes in morphogenesis reshape the signaling environments that activate these regulators remains unknown. Across vertebrates, primitive myeloid cells emerge from bone morphogenetic protein (BMP)-patterned ventral mesoderm through a conserved regulatory program. Here we show that in the annual killifish, Nothobranchius furzeri, a vertebrate with highly derived embryogenesis, neutrophils emerge prior to gastrulation, before ventral mesoderm has formed. Vascular progenitors arise later from ventral mesoderm, whereas myeloid progenitors are largely absent from this tissue. BMP inhibition abolishes pre-gastrula neutrophil specification, while disruption of Nodal-dependent mesendoderm formation does not. These findings reveal that conserved cell type programs can be redeployed within an altered embryonic architecture.

Developmental Biology↗

A statistical framework for inferring genetic requirements from embryo-scale single-cell sequencing experiments

Improvements in single-cell sequencing have enabled phenotyping at organism-scale and molecular resolution, but interpreting such experiments poses computational challenges. Identifying the genes and cell types directly impacted by genetic, chemical, or environmental perturbations requires explicit modeling of lineage relationships amongst many cell types, over time, from datasets with millions of cells collected from thousands of specimens. We describe two software tools, "Hooke" and "Platt", which exploit the rich statistical patterns within single-cell datasets to characterize the direct molecular and cellular consequences of experimental perturbations. We apply Hooke and Platt to a single-cell atlas of thousands of perturbed zebrafish embryos to synthesize a coherent map of lineage dependencies and leverage it to reveal previously unappreciated roles for fate-determining transcription factors. We show that cell type covariation in single-cell datasets is a powerful source of information for inferring how cells depend on genes and one another in the program of vertebrate development.

bioinformatics↗

Embryo-scale single-cell chemical transcriptomics reveals dependencies between cell types and signaling pathways

Organogenesis is a highly organized process that is conserved across vertebrates and is heavily dependent on intercellular signaling to achieve cell type identity. We lack a comprehensive understanding of how developing cell types in each organ and tissue depend on developmental signaling pathways. To address this gap in knowledge, we captured the molecular consequences of inhibiting each of the seven major developmental signaling pathways in zebrafish, using large-scale whole embryo single cell RNA-seq from over two million cells. This approach allowed us to detect signaling pathway regulation even in very rare cell types. By focusing on the development of the pectoral fin, we uncovered two new cell types (distal mesenchyme and tenocytes) and multiple novel signaling dependencies during pectoral fin development. This resource serves as a valuable tool for investigators seeking to rapidly assess the role of the major signaling pathways during the formation of their tissue of interest.

developmental biology↗