Regulation of Stem Cell Fate: Molecular Control of Pluripotent Stem Cells

Animals capable of whole-body regeneration carry a large pool of somatic pluripotent stem cells. During regeneration, pluripotent stem cells can self-renew, proliferate, and differentiate into any cell type. However, the molecular control of these stem cells is poorly understood. To establish a new model system for molecular studies, we first sequenced the genome of a highly regenerative acoel worm. We then studied stem cell regulation in this acoel using single-cell and epigenetic approaches.

• Hulett RE†, Kimura JO†, Bolaños DM†, Luo YJ†, Rivera-Lopez C, Ricci L, Srivastava M (2023) Acoel single-cell atlas reveals expression dynamics and heterogeneity of adult pluripotent stem cells. Nature Communications 14, 2612. (†contributed equally) | Link

• Gehrke AR, Neverett E, Luo YJ, Brandt A, Ricci L, Hulett RE, Gompers A, Ruby JG, Rokhsar DS, Reddien PW, Srivastava M (2019) Acoel genome reveals the regulatory landscape of whole-body regeneration. Science 363, eaau6173. | Link

Evolution of Animal Genomes: Comparative Genomics and Transcriptomics of Lophotrochozoans

Brachiopods (lamp shells), phoronids (horseshoe worms), and nemerteans (ribbon worms) are closely related lophotrochozoans. They are poorly studied despite their importance in ecology, evolution, and paleontology. We decoded the genomes of the brachiopod Lingula anatina, the phoronid Phoronis australis, and the nemertean Notospermus geniculatus to gain insights into animal genome evolution. We showed that Lingula lacks genes involved in bone formation, suggesting an independent origin of their phosphate biominerals. We found that lophotrochozoans share many gene families with deuterostomes, implying that lophotrochozoans retain a core set of bilaterian gene repertoire. Based on transcriptomic analyses, we also discovered a possible common origin of bilaterian head patterning. Together, our study reveals a dual nature of lophotrochozoans in which bilaterian-conserved and lineage-specific features shape the evolution of their genomes.

• Luo YJ, Kanda M, Koyanagi R, Hisata K, Akiyama T, Sakamoto H, Sakamoto T, Satoh N (2018) Nemertean and phoronid genomes reveal lophotrochozoan evolution and the origin of bilaterian heads. Nature Ecology & Evolution 2, 141–151. | Link

• Luo YJ, Takeuchi T, Koyanagi R, Yamada L, Kanda M, Khalturina M, Fujie M, Yamasaki S, Endo K, Satoh N (2015) The Lingula genome provides insights into brachiopod evolution and the origin of phosphate biomineralization. Nature Communications 6, 8301. | Link

Evolution of Gene Regulatory Networks in Deuterostomes: Axial Patterning in Sea Urchins

Through immunolocalization of a phospho-Smad1/5 antibody, we found that BMP signaling is asymmetrically activated on the left side of the sea urchin larva in the first asymmetrical structure, hydroporic canal. By perturbing BMP signals using pharmaceutical treatments and morpholinos, we showed that BMP signals activate expressions of several transcription factors, which are required for the formation of the hydroporic canal. Our findings suggest that there is a deep evolutionary origin of opposing BMP and Nodal signaling in patterning left–right axis in deuterostomes.

• Luo YJ, Su YH (2012) Opposing Nodal and BMP signals regulate left–right asymmetry in the sea urchin larva. PLOS Biology 10, e1001402. | Link

• Chen JH, Luo YJ, Su YH (2011) The dynamic gene expression patterns of transcription factors constituting the sea urchin aboral ectoderm gene regulatory network. Developmental Dynamics 240, 250–260. | Link

Specification of  Germlines and Sensory Neurons in Chordates: Cell Fate Specification in Amphioxus

Amphioxus is a fish-like basal chordate. It occupies a key position to our understanding of the evolution and development of vertebrates. To study the roles of localized RNAs during germline specification, we quantified the aggregation of the structure so-called pole plasm, which contains Piwi-interacting RNAs including vasa and nanos mRNAs in fertilized eggs. By separating blastomeres at the two-cell stage, we found that absence of inheritance of the pole plasm in one of the twin embryos results in a defect of larval tail development. This observation indicates that the function of Vasa-positive cells derived from pole plasm is also required for differentiation and growth of somatic structures. Furthermore, to study neural specification, we reconstructed a three-dimensional neural structure of the  larva and identified an increase of clustered GABA-positive peripheral neurons after perturbing Notch signaling. Our results also showed that BMP signaling functions upstream of Notch signaling to induce a ventral neurogenic domain. We hypothesize a conserved function for BMP signaling in promoting peripheral neuron formation across bilaterians.

• Zhang QJ†, Luo YJ†, Wu HR, Chen YT, Yu JK (2013) Expression of germline markers in three species of amphioxus supports a preformation mechanism of germ cell development in cephalochordates. EvoDevo 4, 17. | Link (†contributed equally)

• Lu TM, Luo YJ, Yu JK (2012) BMP and Delta/Notch signaling control the development of amphioxus epidermal sensory neurons: insights into the evolution of the peripheral sensory system. Development 139, 2020–2030. | Link

Coral–Dinoflagellate Endosymbiosis: Dynamics of the Lipid Content Between Corals and Algae

Coral–dinoflagellate endosymbiosis is the phenomenon in which algal symbionts live inside the animal host cells. The endosymbiosis occurs specifically in the inner tissue layer, the gastrodermis. To study symbiotic cells, we developed a method to isolate tissue layers in corals. Through this technique, we found that a lipid storage organelle, lipid body, shows a dynamic lipid change in the coral cells under continual light or dark treatments . Using ratiometric imaging with a fluorescent probe, Nile red, we analyzed the content of polar and neutral lipids in the lipid bodies. After inducing coral bleaching, we found a depletion of neutral lipids in the lipid bodies. This result suggests that morphological and compositional changes of lipid bodies reflect the symbiotic status.

• Luo YJ, Wang LH, Chen WNU, Peng SE, Tzen JTC, Hsiao YY, Huang HJ, Fang LS, Chen CS (2009) Ratiometric imaging of gastrodermal lipid bodies in coral–dinoflagellate endosymbiosis. Coral Reefs 28, 289–301. | Link

• Peng SE, Luo YJ, Huang HJ, Lee IT, Hou LH, Chen WNU, Fang LS, Chen CS (2008) Isolation of tissue layers in hermatypic corals by N-acetylcysteine: morphological and proteomic examinations. Coral Reefs 27, 133–142. | Link