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1. Genetically targeted chemical assembly of functional materials in living cells, tissues, and animals

   https://doi.org/10.1126/science.aay4866  

   Liu, Jia ; Kim, Yoon Seok ; Richardson, Claire E. ; Tom, Ariane ; Ramakrishnan, Charu ; Birey, Fikri ; Katsumata, Toru ; Chen, Shucheng ; Wang, Cheng ; Wang, Xiao ; et al ( March 2020 , Science)

   null (Ed.)

   The structural and functional complexity of multicellular biological systems, such as the brain, are beyond the reach of human design or assembly capabilities. Cells in living organisms may be recruited to construct synthetic materials or structures if treated as anatomically defined compartments for specific chemistry, harnessing biology for the assembly of complex functional structures. By integrating engineered-enzyme targeting and polymer chemistry, we genetically instructed specific living neurons to guide chemical synthesis of electrically functional (conductive or insulating) polymers at the plasma membrane. Electrophysiological and behavioral analyses confirmed that rationally designed, genetically targeted assembly of functional polymers not only preserved neuronal viability but also achieved remodeling of membrane properties and modulated cell type–specific behaviors in freely moving animals. This approach may enable the creation of diverse, complex, and functional structures and materials within living systems. 

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2. In situ genetically targeted chemical assembly of polymers on living neuronal membranes

   Anqi Zhang, Kang Yong ( December 2022 , bioRxiv)

   Multicellular biological systems, most notably living neural networks, exhibit highly complex physical organization properties that pose challenges for building cell-specific and biocompatible interfaces. We developed a novel approach to genetically program cells to chemically assemble artificial structures that modify the electrical properties of neurons in situ, opening up the possibility of minimally-invasive cell-specific interfaces with neural circuits in living animals. However, the efficiency and biocompatibility of this approach were challenged by limited membrane targeting of the constructed material. Here, we report a method with significantly improved molecular construct properties, which expresses highly localized enzymes targeted to the plasma membrane of primary neurons with minimal intracellular retention. Polymers synthesized in situ by this approach form dense clusters on the targeted cell membrane, and neurons remain viable after polymerization. This platform can be readily extended to incorporate a broad range of materials onto the surface membranes of specific cells within complex tissues, using chemistry that may further enable the next generation of interfaces with living biological systems. 

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3. The genome of the colonial hydroid Hydractinia reveals their stem cells use a toolkit of genes shared with all animals

   Schnitzler, Christine E. ; Chang, E. Sally ; Waletich, Justin ; Quiroga-Artigas, Gonzalo ; Wong, Wai Yee ; Nguyen, Anh-Dao ; Barreira, Sofia N. ; Doonan, Liam ; Gonzalez, Paul ; Koren, Sergey ; et al ( August 2023 , bioRxiv)

   Hydractinia is a colonial marine hydroid that exhibits remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of two Hydractinia species, H. symbiolongicarpus and H. echinata, placing them in a comparative evolutionary framework with other cnidarian genomes. We also generated and annotated a single-cell transcriptomic atlas for adult male H. symbiolongicarpus and identified cell type markers for all major cell types, including key i-cell markers. Orthology analyses based on the markers revealed that Hydractinia's i-cells are highly enriched in genes that are widely shared amongst animals, a striking finding given that Hydractinia has a higher proportion of phylum-specific genes than any of the other 41 animals in our orthology analysis. These results indicate that Hydractinia's stem cells and early progenitor cells may use a toolkit shared with all animals, making it a promising model organism for future exploration of stem cell biology and regenerative medicine. The genomic and transcriptomic resources for Hydractinia presented here will enable further studies of their regenerative capacity, colonial morphology, and ability to distinguish self from non-self. 

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4. Genetically-encoded photosensitizers enable light-controlled polymerization on living neuronal membranes

   Anqi Zhang, Chandan S. ( December 2022 , bioRxiv)

   The ability to record, stimulate, and modify brains of living animals would unlock numerous research opportunities and create potential clinical interventions, but it is difficult to interface with a living neural network without damaging it. We previously reported a novel approach to building neural interfaces, namely: genetically programming cells to build artificial structures to modify the electrical properties of neurons in situ, which opens up the possibility of modifying neural circuits in living animals without surgery. However, the spatiotemporal resolution, efficiency, and biocompatibility of this approach were still limited and lacked selectivity on cell membrane. Here, we demonstrate an approach using genetically-targeted photosensitizers to instruct living cells to synthesize functional materials directly on the plasma membrane under the control of light. Polymers synthesized by this approach were selectively deposited on the membrane of targeted live neurons. This platform can be readily extended to incorporate a broad range of light-controlled reactions onto specific cells, which may enable researchers to grow seamless, dynamic interfaces directly in living animals. 

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5. The genome of the colonial hydroid Hydractinia reveals that their stem cells use a toolkit of evolutionarily shared genes with all animals

   https://doi.org/10.1101/gr.278382.123  

   Schnitzler, Christine E. ; Chang, E. Sally ; Waletich, Justin ; Quiroga-Artigas, Gonzalo ; Wong, Wai Yee ; Nguyen, Anh-Dao ; Barreira, Sofia N. ; Doonan, Liam B. ; Gonzalez, Paul ; Koren, Sergey ; et al ( March 2024 , Genome Research)

   Hydractiniais a colonial marine hydroid that shows remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of twoHydractiniaspecies,Hydractinia symbiolongicarpusandHydractinia echinata, placing them in a comparative evolutionary framework with other cnidarian genomes. We also generated and annotated a single-cell transcriptomic atlas for adult maleH. symbiolongicarpusand identified cell-type markers for all major cell types, including key i-cell markers. Orthology analyses based on the markers revealed thatHydractinia’s i-cells are highly enriched in genes that are widely shared amongst animals, a striking finding given thatHydractiniahas a higher proportion of phylum-specific genes than any of the other 41 animals in our orthology analysis. These results indicate thatHydractinia’s stem cells and early progenitor cells may use a toolkit shared with all animals, making it a promising model organism for future exploration of stem cell biology and regenerative medicine. The genomic and transcriptomic resources forHydractiniapresented here will enable further studies of their regenerative capacity, colonial morphology, and ability to distinguish self from nonself.

    

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