Michael Sars Centre

Publications Christiaen Group

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Latest publications:

Bernadskaya YY, Yue H, Copos C, Christiaen L, Mogilner A (2021) Supracellular organization confers directionality and mechanical potency to migrating pairs of cardiopharyngeal progenitor cells. Elife. 29;10:e70977

Nomaru H, Liu Y, De Bono C, Righelli D, Cirino A, Wang W, Song H, Racedo SE, Dantas AG, Zhang L, Cai CL, Angelini C, Christiaen L, Kelly RG, Baldini A, Zheng D, Morrow BE (2021) Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm. Nat Commun. 17;12(1):6645

Tjärnberg A, Mahmood O, Jackson CA, Saldi GA, Cho K, Christiaen L, Bonneau RA (2021) Optimal tuning of weighted kNN- and diffusion-based methods for denoising single cell genomics data. PLoS Comput Biol., 17(1):e1008569

Lowe EK, Racioppi C, Peyriéras N, Ristoratore F, Christiaen L, Swalla BJ, Stolfi A (2021) A cis-regulatory change underlying the motor neuron-specific loss of Ebf expression in immotile tunicate larvae. Evol Dev., 23(2):72-85

Ohta N, Kaplan N, Ng JT, Gravez BJ, Christiaen L (2020) Asymmetric Fitness of Second-Generation Interspecific Hybrids Between Ciona robusta and Ciona intestinalis. G3: Genes, Genomes, Genetics 10(8):2697-2711

Vitrinel B, Iannitelli DE, Mazzoni EO, Christiaen L, Vogel C (2020) Simple Method to Quantify Protein Abundances from 1000 Cells. ACS Omega, 5(25):15537-15546

Shim WJ, Sinniah E, Xu J, Vitrinel B, Alexanian M, Andreoletti G, Shen S, Sun Y, Balderson B, Boix C, Peng G, Jing N, Wang Y, Kellis M, Tam PPL, Smith A, Piper M, Christiaen L, Nguyen Q, Bodén M, Palpant NJ (2020) Conserved Epigenetic Regulatory Logic Infers Genes Governing Cell Identity. Cell Syst., 11(6):625-639

Selected Citations from bioRxiv

Vitrinel, Burcu, Christine Vogel, and Lionel Christiaen.
"Rnf149-related is an FGF/MAPK-independent regulator of pharyngeal muscle fate specification."

bioRxiv (2022): 2022.01.07.475354. Web. 26 Jan. 2022. During embryonic development, cell fate specification gives rise to dedicated lineages that underlie tissue formation. In olfactores, which comprise tunicates and vertebrates, the cardiopharyngeal field is formed by multipotent progenitors to both cardiac and branchiomeric muscles. The ascidian Ciona is a powerful model to study the cardiopharyngeal fate specification with cellular resolution, as only 2 pairs of cardiopharyngeal multipotent progenitors give rise to the heart and to pharyngeal muscles (aka atrial siphon muscles, ASM). These progenitors are multilineage primed, in as much as they express a combination of early ASM- and heart-specific transcripts that become restricted to their corresponding precursors, following oriented asymmetric divisions. Here, we identify the primed gene Rnf149-related (Rnf149-r), which becomes restricted to the heart progenitors, but appears to regulate pharyngeal muscle fate specification in the cardiopharyngeal lineage. CR ISPR/Cas9-mediated loss knock-out of Rnf149-r function impairs atrial siphon muscle morphogenesis, and down-regulates Tbx1/10 and Ebf, two key determinants of the pharyngeal muscle fate, while upregulating heart-specific gene expression. These phenotypes are reminiscent of loss of FGF-MAPK signaling in the cardiopharyngeal lineage, and integrated analysis of lineage-specific bulk RNA-seq profiling of loss-of-function perturbations identified a significant overlap between FGF-MAPK and Rnf149-r targets. However, functional interaction assays suggested the Rnf149-r does not directly modulate the activity of the FGF-MAPK-Ets1/2 pathway. Instead, we propose that Rnf149-r acts both in parallel to the FGF-MAPK signaling on shared targets, as well as on FGF-MAPK-independent targets through (a) separate pathway(s).Competing Interest StatementThe authors have declared no competing interest. 


Ohta, Naoyuki, and Lionel Christiaen.
"Cellular remodeling and JAK inhibition promote zygotic gene expression in the Ciona germline."

bioRxiv (2021): 2021.07.12.452040. Web. 26 Jan. 2022. During development, remodeling of the cellular transcriptome and proteome underlies cell fate decisions and, in somatic lineages, transcription control is a major determinant of fateful biomolecular transitions. By contrast, early germline fate specification in numerous vertebrate and invertebrate species relies extensively on RNA-level regulation, exerted on asymmetrically inherited maternal supplies, with little-to-no zygotic transcription. However delayed, a maternal-to-zygotic transition is nevertheless poised to complete the deployment of pre-gametic programs in the germline. Here, we focused on early germline specification in the tunicate Ciona to study zygotic genome activation. We first demonstrate that a peculiar cellular remodeling event excludes localized postplasmic mRNAs, including Pem-1, which encodes the general inhibitor of transcription. Subsequently, zygotic transcription begins in Pem-1-negative primordial germ cells (PGCs), as revealed by his tochemical detection of elongating RNA Polymerase II (RNAPII), and nascent transcripts from the Mef2 locus. Using PGC-specific Mef2 transcription as a read-out, we uncovered a provisional antagonism between JAK and MEK/BMPRI/GSK3 signaling, which controls the onset of zygotic gene expression, following cellular remodeling of PGC. We propose a 2-step model for the onset of zygotic transcription in the Ciona germline, which relies on successive cellular remodeling and JAK inhibition, and discuss the significance of germ plasm dislocation and remodeling in the context of developmental fate specification.Competing Interest StatementThe authors have declared no competing interest.