Biology subjects

Primack, A. S.

Publications and source records attributed to Primack, A. S..

5 recordsLinked to original sources

bioRxiv2023

Differentiation trajectories of the Hydra nervous system reveal transcriptional regulators of neuronal fate

Hydra vulgaris, a cnidarian with a simple nerve net, is an emerging model for developmental, regenerative, and functional neuroscience. Its genetic tractability and capacity for whole-system imaging make it well suited for studying neuron replacement, regeneration, and neural circuit function. Here, we present the most comprehensive molecular and spatial characterization of the H. vulgaris nervous system to date. Using single-cell RNA sequencing, we identified eight neuron types, each defined by distinct neuropeptide expression, and further resolved these into fifteen transcriptionally distinct subtypes with unique spatial distributions and morphologies. To investigate the gene regulatory networks underlying neuronal differentiation, we applied trajectory inference, identified key transcription factors, and performed ATAC-seq on sorted neurons to map chromatin accessibility. All datasets are available through an interactive, user-friendly web portal to support broad use by the research community. Together, these resources provide a foundation for uncovering molecular mechanisms that govern nervous system development, homeostasis, and regeneration in H. vulgaris. Summary StatementHydra vulgaris is a model for regenerative and functional neuroscience. This study identifies fifteen neuron subtypes using scRNA-seq, maps spatial distributions, explores regulatory mechanisms, and provides an accessible web portal.

developmental biology↗

bioRxiv2022

New Hydra Genomes Reveal Conserved Principles of Hydrozoan Transcriptional Regulation

The epithelial and interstitial stem cells of the freshwater polyp Hydra are the best characterized stem cell systems in any cnidarian, providing valuable insight into cell type evolution and the origin of stemness in animals. However, little is known about the transcriptional regulatory mechanisms that determine how these stem cells are maintained and how they give rise to their diverse differentiated progeny. To address such questions, a thorough understanding of transcriptional regulation in Hydra is needed. To this end, we generated extensive new resources for characterizing transcriptional regulation in Hydra, including new genome assemblies for Hydra oligactis and the AEP strain of Hydra vulgaris, an updated whole-animal single-cell RNA-seq atlas, and genome-wide maps of chromatin interactions, chromatin accessibility, sequence conservation, and histone modifications. These data revealed the existence of large chromatin interaction domains in the Hydra genome that likely influence transcriptional regulation in a manner distinct from topologically associating domains in bilaterians. We also uncovered the transcriptomic profiles of two previously molecularly uncharacterized cell types, isorhiza-containing nematocytes and somatic gonad ectoderm. We identified novel candidate regulators of cell-type-specific transcription, several of which have likely been conserved at least since the divergence of Hydra and the jellyfish Clytia hemisphaerica over 200 million years ago. The resources generated in this study, which collectively represent the most comprehensive characterization of transcriptional regulation in a cnidarian to date, are accessible through a newly created genome portal, available at research.nhgri.nih.gov/HydraAEP/.

developmental biology↗

bioRxiv2020

Multiple nerve rings coordinate Hydra mechanosensory behavior

Hydra vulgaris is an emerging model organism for neuroscience due to its small size, transparency, genetic tractability, and regenerative nervous system; however, fundamental properties of its sensorimotor behaviors remain unknown. Here, we use microfluidic devices combined with fluorescent calcium imaging and surgical resectioning to study how the diffuse nervous system coordinates Hydras mechanosensory response. Mechanical stimuli cause animals to contract, and we find this response relies on at least two distinct networks of neurons in the oral and aboral regions of the animal. Different activity patterns arise in these networks depending on whether the animal is contracting spontaneously or contracting in response to mechanical stimulation. Together, these findings improve our understanding of how Hydras diffuse nervous system coordinates sensorimotor behaviors. These insights help reveal how sensory information is processed in an animal with a diffuse, radially symmetric neural architecture unlike the dense, bilaterally symmetric nervous systems found in most model organisms.

neuroscience↗

bioRxiv2018

Stem cell differentiation trajectories in Hydra resolved at single-cell resolution

The adult Hydra polyp continuously renews all of its cells using three separate stem cell populations, but the genetic pathways enabling homeostatic tissue maintenance are not well understood. We used Drop-seq to sequence transcriptomes of 24,985 single Hydra cells and identified the molecular signatures of a broad spectrum of cell states, from stem cells to terminally differentiated cells. We constructed differentiation trajectories for each cell lineage and identified the transcription factors expressed along these trajectories, thus creating a comprehensive molecular map of all developmental lineages in the adult animal. We unexpectedly found that neuron and gland cell differentiation transits through a common progenitor state, suggesting a shared evolutionary history for these secretory cell types. Finally, we have built the first gene expression map of the Hydra nervous system. By producing a comprehensive molecular description of the adult Hydra polyp, we have generated a resource for addressing fundamental questions regarding the evolution of developmental processes and nervous system function.

developmental biology↗

bioRxiv2017

Hammondia hammondi has a developmental program in vitro that mirrors its stringent two host life cycle

Hammondia hammondi is the nearest relative of Toxoplasma gondii, but unlike T. gondii is obligately heteroxenous. We have compared H. hammondi and T. gondii development in vitro and identified multiple H. hammondi-specific growth states. Despite replicating slower than T. gondii, H. hammondi was resistant to pH-induced tissue cyst formation early after excystation. However, in the absence of stress H. hammondi spontaneously converted to a terminally differentiated tissue cyst stage while T. gondii did not. Cultured H. hammondi could infect new host cells for up to 8 days following excystation, and this period was exploited to generate stably transgenic H. hammondi. Coupled with RNAseq analyses, our data clearly show that H. hammondi zoites grow as stringently regulated life stages that are fundamentally distinct from T. gondii tachyzoites and bradyzoites.

microbiology↗