A Comprehensive Transcriptomic and Proteomic Analysis of Hydra Head Regeneration

Abstract

The cnidarian freshwater polyp Hydra sp. exhibits an unparalleled regeneration capacity in the animal kingdom. Using an integrative transcriptomic and stable isotope labeling by amino acids in cell culture proteomic/phosphoproteomic approach, we studied stem cell-based regeneration in Hydra polyps. As major contributors to head regeneration, we identified diverse signaling pathways adopted for the regeneration response as well as enriched novel genes. Our global analysis reveals two distinct molecular cascades: an early injury response and a subsequent, signaling driven patterning of the regenerating tissue. A key factor of the initial injury response is a general stabilization of proteins and a net upregulation of transcripts, which is followed by a subsequent activation cascade of signaling molecules including Wnts and transforming growth factor (TGF) beta-related factors. We observed moderate overlap between the factors contributing to proteomic and transcriptomic responses suggesting a decoupled regulation between the transcriptional and translational levels. Our data also indicate that interstitial stem cells and their derivatives (e.g., neurons) have no major role in Hydra head regeneration. Remarkably, we found an enrichment of evolutionarily more recent genes in the early regeneration response, whereas conserved genes are more enriched in the late phase. In addition, genes specific to the early injury response were enriched in transposon insertions. Genetic dynamicity and taxon-specific factors might therefore play a hitherto underestimated role in Hydra regeneration.

Generic and context-dependent gene modulations duringHydrawhole body regeneration

“…Previous reports in Hydra Petersen et al, 2015;Gufler et al, 2018) and planaria (Wenemoser et al, 2012) identified genes activated early after injury, irrespective of the position and expected fate of the stump. These genes were associated with woundhealing, immunity, or even patterning as b-catenin targets that were shown to behave similarly at the transcriptional level during the first hours of regeneration (Gufler et al, 2018).…”

“…In bilaterians, unbiased transcriptomics/proteomics approaches have proven useful to determine the genetic programs involved in the regeneration of complex structures, such as body parts in planarians (Kao et al, 2013) or Hydra (Petersen et al, 2015), appendages in zebrafish, lizards, salamanders (Hutchins et al, 2014;Bryant et al, 2017;Rabinowitz et al, 2017), heart in zebrafish (Lai et al, 2017) and mammals (Quaife-Ryan et al, 2017), lens in salamanders (Looso et al, 2013). These programs drive wound healing, stem cell recruitment and/or somatic tissue re-specification and 3D-patterning, the latter including the re-activation of specific developmental patterning mechanisms.…”

Profiling of adhesive-related genes in the freshwater cnidarianHydra magnipapillataby transcriptomics and proteomics

“…The Illumina sequencing effort used in the present work led to a reliable transcriptome assembly and differential gene expression results. While undertaking the present work, two transcriptomes for the H. magnipapillata 105 strain were published from different sources (Juliano et al 2014; Petersen et al 2015). There is a considerable discrepancy in the number of assembled transcripts between the different works (27,128 transcripts, Juliano et al (2014); 36,338 transcripts, Petersen et al (2015); and 55,849 transcripts, present work).…”

“…The use of different strategies for the transcriptome assembly is a hindrance for a more detailed comparison. For example, Petersen et al (2015) set a number of 400 bp as cut-off for their assembly while the present work set 200 bp. In another Hydra strain ( Hydra vulgaris strain Basel), RNAseq transcriptome yielded 48,909 assembled transcripts (Wenger & Galliot 2013).…”

Regulation of AP-1 by MAPK Signaling in Metal-Stressed Sea Anemone

“…Among our findings, we have identified rapid activation of several immediate-early response genes such as the transcription factors early growth response1 ( egr1 ) and fos . Furthermore, fos transcript was shown to be up-regulated by injury in Nematostella [26], during head regeneration in Hydra and during metamorphosis of coral larvae [27-29]. …”