New Hydra genomes reveal conserved principles of hydrozoan transcriptional regulation

Abstract

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/.

Evolution of homology: From archetype towards a holistic concept of cell type

“…In vertebrates, this reprogramming is essential to convert terminally differentiated gametes to the totipotent zygote producing an embryo, whereas totipotency itself can be captured and maintained in vitro from embryonic cells by sustained chemical inhibition of just a few key enzymes, mainly chromatin modifiers implicated in gene repression via histone methylation and deacetylation (Xu et al, 2022). Recent cellular transcriptomic evidence reveals chromatin modifiers among the markers of animal stem cells on a broad evolutionary timescale, which suggests a pan‐metazoan epigenetic control of cell stemness (see above; Cazet et al, 2022; Sogabe et al, 2019; Tarashansky et al, 2021). It is becoming clear that epigenetic modifications are universally employed by most animals and beyond for executing deeply conserved regulatory functions, including expression control of evolutionarily old genes, as well as that these marks play vital evolutionary roles by establishing epigenetic memories inheritable across generations (Keller et al, 2016; Vogt, 2022; Zemach et al, 2010).…”

“…This means that certain portions of their underlying GRNs become shared by cell types via particular evolutionary mechanisms, whereas, at least, the ‘many‐to‐many’ structure of similarity cannot be explained by linear evolutionary divergence of cell types with time. A marginal illustration are epi‐ and endothelia (Cazet et al, 2022; Wang et al, 2021): these cell types are highest derived in terms of both their underlying gene content and age, display fewest one‐to‐one cross‐species similarities and many inter‐type connections, suggesting their role as a major reservoir of cell type innovation. The epithelial ‘phylogeny’ has been particularly demonstrated to have a more nonbinary, network‐like structure, where strongest connections across phyla do not span continuous paths in the species tree, thus precluding its explanation by vertical evolutionary descent.…”

“…Deep molecular roots of animal cell stemness also become elucidated from a comparison of whole‐body single‐cell atlases of two hydrozoan cnidarians that diverged over 200 Mya and represent different, polypoid and medusoid, metagenetic life cycle generations (Cazet et al, 2022). The study employed the cell type ‘alignment’ procedure developed in Tarashansky et al (2021), to quantitatively match cell types between species, and used a phylostratigraphic approach (Domazet‐Lošo & Tautz, 2010; Domazet‐Lošo et al, 2007) to assign clade‐specific ages to genes maintaining the cell types.…”

“…That is, the emergence of neurons themselves would certainly not be described by hierarchic transcription. In fact, this situation is the most common in cell‐type comparisons, with epi‐ and endothelia being an extreme example, where the types exhibit derived and interspersed patterns in cell‐type alignments and clustering (Cazet et al, 2022; Tarashansky et al, 2021) or fall widely across the clades of a proxy cell type phylogeny, both within‐ and between‐species (Wang et al, 2021). The deeper in time, the more entangled this exchange becomes, eventually forming a dense network of relationships, which means that the earliest history of cell types will remain obscure.…”

“…Recent cellular transcriptomic evidence reveals chromatin modifiers among the markers of animal stem cells on a broad evolutionary timescale, which suggests a pan-metazoan epigenetic control of cell stemness (see above; Cazet et al, 2022;Sogabe et al, 2019;Tarashansky et al, 2021). It is becoming clear that epigenetic modifications are universally employed by most animals and beyond for executing deeply conserved regulatory functions, including expression control of evolutionarily old genes, as well as that these marks play vital evolutionary roles by establishing epigenetic memories inheritable across generations (Keller et al, 2016;Vogt, 2022;Zemach et al, 2010).…”