Single cell biology-a Keystone Symposia report

Jennifer Cable¹, Michael B Elowitz^{2

3}, Ana I Domingos^{4

5}, Naomi Habib^{6

7}, Shalev Itzkovitz⁸, Homaira Hamidzada⁹, Michael S Balzer¹⁰, Itai Yanai¹¹, Prisca Liberali¹², Jessica Whited¹³, Aaron Streets^{14

15}, Long Cai², Andrew B Stergachis¹⁶, Clarice Kit Yee Hong^{17

18}, Leeat Keren^{8

19}, Martin Guilliams²⁰, Uri Alon²¹, Alex K Shalek²², Regan Hamel²³, Sarah J Pfau²⁴, Arjun Raj^{25

26}, Stephen R Quake^{15

27

28}, Nancy R Zhang²⁹, Jean Fan³⁰, Cole Trapnell³¹, Bo Wang^{27

32}, Noah F Greenwald¹⁹, Roser Vento-Tormo³³, Silvia D M Santos³⁴, Sabrina L Spencer³⁵, Hernan G Garcia³⁶, Geethika Arekatla³⁷, Federico Gaiti³⁸, Rinat Arbel-Goren³⁹, Steffen Rulands⁴⁰, Jan Philipp Junker⁴¹, Allon M Klein⁴², Samantha A Morris^{18

43}, John I Murray²⁵, Kate E Galloway⁴⁴, Michael Ratz⁴⁵, Merrit Romeike⁴⁶

Affiliations

¹ PhD Science Writer, New York, New York.
² Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California.
³ Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California.
⁴ Department of Physiology, Anatomy & Genetics, Oxford University, Oxford, United Kingdom.
⁵ The Howard Hughes Medical Institute, New York, New York.
⁶ Cell Circuits Program, Broad Institute, Cambridge, Massachusetts.
⁷ Edmond & Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁸ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
⁹ Toronto General Hospital Research Institute, University Health Network; Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research and Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Renal, Electrolyte, and Hypertension Division, Department of Medicine and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
¹¹ Institute for Computational Medicine, NYU Langone Health, New York, New York.
¹² Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
¹³ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts.
¹⁴ Department of Bioengineering and Center for Computational Biology, University of California, Berkeley, Berkeley, California.
¹⁵ Chan Zuckerberg Biohub, San Francisco, California.
¹⁶ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington; and Brotman Baty Institute for Precision Medicine, Seattle, Washington.
¹⁷ Edison Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, Missouri.
¹⁸ Department of Genetics, Washington University in St. Louis, St. Louis, Missouri.
¹⁹ Department of Pathology, School of Medicine, Stanford University, Stanford, California.
²⁰ Laboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, and Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
²¹ Faculty of Sciences, Department of Human Biology, University of Haifa, Haifa, Israel.
²² Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts.
²³ Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom.
²⁴ Department of Neurobiology, Harvard Medical School, Boston, Massachusetts.
²⁵ Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
²⁶ Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania.
²⁷ Department of Bioengineering, Stanford University, Stanford, California.
²⁸ Department of Applied Physics, Stanford University, Stanford, California.
²⁹ Graduate Group in Genomics and Computational Biology and Department of Statistics, University of Pennsylvania, Philadelphia, Pennsylvania.
³⁰ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
³¹ Department of Genome Sciences, University of Washington School of Medicine; Brotman Baty Institute for Precision Medicine; and Allen Discovery Center for Cell Lineage Tracing, Seattle, Washington.
³² Department of Developmental Biology, Stanford University School of Medicine, Stanford, California.
³³ Wellcome Sanger Institute, Cambridgeshire, United Kingdom.
³⁴ The Francis Crick Institute, London, United Kingdom.
³⁵ Department of Biochemistry and BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado.
³⁶ Department of Physics; Biophysics Graduate Group; Department of Molecular and Cell Biology; and Institute for Quantitative Biosciences-QB3, University of California at Berkeley, Berkeley, California.
³⁷ ETH Zurich, Zurich, Switzerland.
³⁸ New York Genome Center and Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
³⁹ Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel.
⁴⁰ Max Planck Institute for the Physics of Complex Systems, and Center for Systems Biology Dresden, Dresden, Germany.
⁴¹ Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
⁴² Department of Systems Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.
⁴³ Department of Developmental Biology and Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, Missouri.
⁴⁴ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
⁴⁵ Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden.
⁴⁶ Max Perutz Laboratories Vienna, University of Vienna, Vienna, Austria.

PMID: 34605044
DOI: 10.1111/nyas.14692

Review

Single cell biology-a Keystone Symposia report

Jennifer Cable et al. Ann N Y Acad Sci. 2021 Dec.

. 2021 Dec;1506(1):74-97.

doi: 10.1111/nyas.14692. Epub 2021 Oct 3.

Authors

Affiliations

¹ PhD Science Writer, New York, New York.
² Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California.
³ Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California.
⁴ Department of Physiology, Anatomy & Genetics, Oxford University, Oxford, United Kingdom.
⁵ The Howard Hughes Medical Institute, New York, New York.
⁶ Cell Circuits Program, Broad Institute, Cambridge, Massachusetts.
⁷ Edmond & Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁸ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
⁹ Toronto General Hospital Research Institute, University Health Network; Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research and Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Renal, Electrolyte, and Hypertension Division, Department of Medicine and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
¹¹ Institute for Computational Medicine, NYU Langone Health, New York, New York.
¹² Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
¹³ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts.
¹⁴ Department of Bioengineering and Center for Computational Biology, University of California, Berkeley, Berkeley, California.
¹⁵ Chan Zuckerberg Biohub, San Francisco, California.
¹⁶ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington; and Brotman Baty Institute for Precision Medicine, Seattle, Washington.
¹⁷ Edison Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, Missouri.
¹⁸ Department of Genetics, Washington University in St. Louis, St. Louis, Missouri.
¹⁹ Department of Pathology, School of Medicine, Stanford University, Stanford, California.
²⁰ Laboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, VIB-UGent Center for Inflammation Research, and Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
²¹ Faculty of Sciences, Department of Human Biology, University of Haifa, Haifa, Israel.
²² Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts.
²³ Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom.
²⁴ Department of Neurobiology, Harvard Medical School, Boston, Massachusetts.
²⁵ Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
²⁶ Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania.
²⁷ Department of Bioengineering, Stanford University, Stanford, California.
²⁸ Department of Applied Physics, Stanford University, Stanford, California.
²⁹ Graduate Group in Genomics and Computational Biology and Department of Statistics, University of Pennsylvania, Philadelphia, Pennsylvania.
³⁰ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
³¹ Department of Genome Sciences, University of Washington School of Medicine; Brotman Baty Institute for Precision Medicine; and Allen Discovery Center for Cell Lineage Tracing, Seattle, Washington.
³² Department of Developmental Biology, Stanford University School of Medicine, Stanford, California.
³³ Wellcome Sanger Institute, Cambridgeshire, United Kingdom.
³⁴ The Francis Crick Institute, London, United Kingdom.
³⁵ Department of Biochemistry and BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado.
³⁶ Department of Physics; Biophysics Graduate Group; Department of Molecular and Cell Biology; and Institute for Quantitative Biosciences-QB3, University of California at Berkeley, Berkeley, California.
³⁷ ETH Zurich, Zurich, Switzerland.
³⁸ New York Genome Center and Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
³⁹ Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel.
⁴⁰ Max Planck Institute for the Physics of Complex Systems, and Center for Systems Biology Dresden, Dresden, Germany.
⁴¹ Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
⁴² Department of Systems Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.
⁴³ Department of Developmental Biology and Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, Missouri.
⁴⁴ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
⁴⁵ Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden.
⁴⁶ Max Perutz Laboratories Vienna, University of Vienna, Vienna, Austria.

PMID: 34605044
DOI: 10.1111/nyas.14692

Abstract

Single cell biology has the potential to elucidate many critical biological processes and diseases, from development and regeneration to cancer. Single cell analyses are uncovering the molecular diversity of cells, revealing a clearer picture of the variation among and between different cell types. New techniques are beginning to unravel how differences in cell state-transcriptional, epigenetic, and other characteristics-can lead to different cell fates among genetically identical cells, which underlies complex processes such as embryonic development, drug resistance, response to injury, and cellular reprogramming. Single cell technologies also pose significant challenges relating to processing and analyzing vast amounts of data collected. To realize the potential of single cell technologies, new computational approaches are needed. On March 17-19, 2021, experts in single cell biology met virtually for the Keystone eSymposium "Single Cell Biology" to discuss advances both in single cell applications and technologies.

Keywords: development; differentiation; lineage tracing; reprogramming; single cell sequencing; spatial transcriptomics.

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References

1. Zhu, R., J.M. del Rio-Salgado, J. Garcia-Ojalvo, et al. 2021. Synthetic multistability in mammalian cells. bioRxiv. https://doi.org/10.1101/2021.02.10.430659.
1. Su, C.J., A. Murugan, J.M. Linton, et al. 2020. Ligand-receptor promiscuity enables cellular addressing. bioRxiv. https://doi.org/10.1101/2020.12.08.412643.
1. Ma, Y., M.W. Budde, M.N. Mayalu, et al. 2020. Synthetic mammalian signaling circuits for robust cell population control. bioRxiv. https://doi.org/10.1101/2020.09.02.278564.
1. Zeng, W., R.M. Pirzgalska, M.M.A. Pereira, et al. 2015. Sympathetic neuro-adipose connections mediate leptin-driven lipolysis. Cell 163: 84-94.
1. Pirzgalska, R.M., E. Seixas, J.S. Seidman, et al. 2017. Sympathetic neuron-associated macrophages contribute to obesity by importing and metabolizing norepinephrine. Nat. Med. 23: 1309-1318.

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Single cell biology-a Keystone Symposia report

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Single cell biology-a Keystone Symposia report

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