PMID- 35195068 OWN - NLM STAT- In-Process VI - 11 TI - Spatial transcriptomic and single-nucleus analysis reveals heterogeneity in a gigantic single-celled syncytium. CI - © 2022, Gerber et al. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Elife JT - eLife JID - 101579614 IS - 2050-084X (Electronic) LID - 10.7554/eLife.69745 [doi] LID - e69745 [pii] FAU - Gerber, Tobias AU - Gerber T AUID- ORCID: 0000-0001-8456-5495 AD - Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. FAU - Loureiro, Cristina AU - Loureiro C AD - Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland. FAU - Schramma, Nico AU - Schramma N AD - Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany. FAU - Chen, Siyu AU - Chen S AD - Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany. AD - Physics Department, Technical University of Munich, München, Germany. FAU - Jain, Akanksha AU - Jain A AD - Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland. FAU - Weber, Anne AU - Weber A AD - Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany. FAU - Weigert, Anne AU - Weigert A AD - Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. FAU - Santel, Malgorzata AU - Santel M AD - Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland. FAU - Alim, Karen AU - Alim K AUID- ORCID: 0000-0002-2527-5831 AD - Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany. AD - Physics Department, Technical University of Munich, München, Germany. FAU - Treutlein, Barbara AU - Treutlein B AUID- ORCID: 0000-0002-3299-5597 AD - Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. AD - Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland. FAU - Camp, J Gray AU - Camp JG AUID- ORCID: 0000-0003-3295-1225 AD - Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. AD - Roche Institute for Translational Bioengineering (ITB), Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland. AD - University of Basel, Basel, Switzerland. IS - 2050-084X (Linking) SB - IM OTO - NOTNLM OT - *Physarum polycephalum OT - *Single-nucleus RNA-seq OT - *Spatial transcriptomics OT - *cell biology OT - *genetics OT - *genomics OT - *syncytium LR - 20220223 DP - 20220223 DEP - 20220223 AB - In multicellular organisms, the specification, coordination, and compartmentalization of cell types enable the formation of complex body plans. However, some eukaryotic protists such as slime molds generate diverse and complex structures while remaining in a multinucleate syncytial state. It is unknown if different regions of these giant syncytial cells have distinct transcriptional responses to environmental encounters and if nuclei within the cell diversify into heterogeneous states. Here, we performed spatial transcriptome analysis of the slime mold Physarum polycephalum in the plasmodium state under different environmental conditions and used single-nucleus RNA-sequencing to dissect gene expression heterogeneity among nuclei. Our data identifies transcriptome regionality in the organism that associates with proliferation, syncytial substructures, and localized environmental conditions. Further, we find that nuclei are heterogenous in their transcriptional profile and may process local signals within the plasmodium to coordinate cell growth, metabolism, and reproduction. To understand how nuclei variation within the syncytium compares to heterogeneity in single-nucleus cells, we analyzed states in single Physarum amoebal cells. We observed amoebal cell states at different stages of mitosis and meiosis, and identified cytokinetic features that are specific to nuclei divisions within the syncytium. Notably, we do not find evidence for predefined transcriptomic states in the amoebae that are observed in the syncytium. Our data shows that a single-celled slime mold can control its gene expression in a region-specific manner while lacking cellular compartmentalization and suggests that nuclei are mobile processors facilitating local specialized functions. More broadly, slime molds offer the extraordinary opportunity to explore how organisms can evolve regulatory mechanisms to divide labor, specialize, balance competition with cooperation, and perform other foundational principles that govern the logic of life.