Applying single-cell and single-nucleus genomics to studies of cellular heterogeneity and cell fate transitions in the nervous system

Igor Adameyko^{1

2}, Trygve Bakken³, Aparna Bhaduri⁴, Chintan Chhatbar⁵, Mariella G Filbin⁶, David Gate⁷, Hannah Hochgerner⁸, Chang Nam Kim^{9

10}, Jordan Krull^{11

12}, Gioele La Manno¹³, Qingyun Li^{14

15}, Sten Linnarsson¹⁶, Qin Ma^{11

12}, Christian Mayer¹⁷, Vilas Menon¹⁸, Patricia Nano⁴, Marco Prinz^{5

19}, Steve Quake^{20

21

22}, Christopher A Walsh^{23

24

25}, Jin Yang^{14

15}, Omer Ali Bayraktar²⁶, Ozgun Gokce^{27

28}, Naomi Habib²⁹, Genevieve Konopka^{30

31}, Shane A Liddelow^{32

33

34

35}, Tomasz J Nowakowski^{36

37

38

39

40}

Affiliations

¹ Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
² Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
³ Allen Institute for Brain Science, Seattle, WA, USA.
⁴ Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁵ Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
⁶ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, MA, USA.
⁷ The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁸ Faculty of Biotechnology and Food Engineering, Technion Israel Institute of Technology, Haifa, Israel.
⁹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Department of Anatomy, University of California San Francisco, San Francisco, CA, USA.
¹¹ Department of Biomedical Informatics, College of Medicine, the Ohio State University, Columbus, OH, USA.
¹² Pelotonia Institute for Immuno-Oncology, the James Comprehensive Cancer Center, the Ohio State University, Columbus, OH, USA.
¹³ Laboratory of Neurodevelopmental Systems Biology, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
¹⁴ Department of Neuroscience, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
¹⁵ Department of Genetics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
¹⁶ Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
¹⁷ Max Planck Institute for Biological Intelligence, Martinsried, Germany.
¹⁸ Department of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University, New York, NY, USA.
¹⁹ Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
²⁰ Department of Bioengineering, Stanford University, Stanford, CA, USA.
²¹ Department of Applied Physics, Stanford University, Stanford, CA, USA.
²² Chan Zuckerberg Biohub, San Francisco, CA, USA.
²³ Division of Genetics and Genomics, Manton Center for Orphan Disease, Boston Children's Hospital, Boston, MA, USA.
²⁴ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
²⁵ Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
²⁶ Wellcome Sanger Institute, Hinxton, UK. ob5@sanger.ac.uk.
²⁷ Department of Old Age Psychiatry and Cognitive Disorders, University Hospital Bonn, Bonn, Germany. ozgun.goekce@ukbonn.de.
²⁸ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. ozgun.goekce@ukbonn.de.
²⁹ The Edmond and Lily Safra Center for Brain Sciences, the Hebrew University of Jerusalem, Jerusalem, Israel. naomi.habib@mail.huji.ac.il.
³⁰ Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, USA. genevieve.konopka@utsouthwestern.edu.
³¹ Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA. genevieve.konopka@utsouthwestern.edu.
³² Neuroscience Institute, NYU Grossman School of Medicine, New York, NY, USA. shane.liddelow@nyulangone.org.
³³ Department of Neuroscience and Physiology, NYU Grossman School of Medicine, New York, NY, USA. shane.liddelow@nyulangone.org.
³⁴ Parekh Center for Interdisciplinary Neurology, NYU Grossman School of Medicine, New York, NY, USA. shane.liddelow@nyulangone.org.
³⁵ Department of Ophthalmology, NYU Grossman School of Medicine, New York, NY, USA. shane.liddelow@nyulangone.org.
³⁶ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA. tomasz.nowakowski@ucsf.edu.
³⁷ Department of Anatomy, University of California San Francisco, San Francisco, CA, USA. tomasz.nowakowski@ucsf.edu.
³⁸ Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA. tomasz.nowakowski@ucsf.edu.
³⁹ Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA. tomasz.nowakowski@ucsf.edu.
⁴⁰ The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA. tomasz.nowakowski@ucsf.edu.

PMID: 39627588
PMCID: PMC11949301 (available on 2025-12-03)
DOI: 10.1038/s41593-024-01827-9

Review

Applying single-cell and single-nucleus genomics to studies of cellular heterogeneity and cell fate transitions in the nervous system

Igor Adameyko et al. Nat Neurosci. 2024 Dec.

. 2024 Dec;27(12):2278-2291.

doi: 10.1038/s41593-024-01827-9. Epub 2024 Dec 3.

Authors

Affiliations

¹ Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
² Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
³ Allen Institute for Brain Science, Seattle, WA, USA.
⁴ Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁵ Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
⁶ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, MA, USA.
⁷ The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁸ Faculty of Biotechnology and Food Engineering, Technion Israel Institute of Technology, Haifa, Israel.
⁹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Department of Anatomy, University of California San Francisco, San Francisco, CA, USA.
¹¹ Department of Biomedical Informatics, College of Medicine, the Ohio State University, Columbus, OH, USA.
¹² Pelotonia Institute for Immuno-Oncology, the James Comprehensive Cancer Center, the Ohio State University, Columbus, OH, USA.
¹³ Laboratory of Neurodevelopmental Systems Biology, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
¹⁴ Department of Neuroscience, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
¹⁵ Department of Genetics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
¹⁶ Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
¹⁷ Max Planck Institute for Biological Intelligence, Martinsried, Germany.
¹⁸ Department of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University, New York, NY, USA.
¹⁹ Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
²⁰ Department of Bioengineering, Stanford University, Stanford, CA, USA.
²¹ Department of Applied Physics, Stanford University, Stanford, CA, USA.
²² Chan Zuckerberg Biohub, San Francisco, CA, USA.
²³ Division of Genetics and Genomics, Manton Center for Orphan Disease, Boston Children's Hospital, Boston, MA, USA.
²⁴ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
²⁵ Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
²⁶ Wellcome Sanger Institute, Hinxton, UK. ob5@sanger.ac.uk.
²⁷ Department of Old Age Psychiatry and Cognitive Disorders, University Hospital Bonn, Bonn, Germany. ozgun.goekce@ukbonn.de.
²⁸ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. ozgun.goekce@ukbonn.de.
²⁹ The Edmond and Lily Safra Center for Brain Sciences, the Hebrew University of Jerusalem, Jerusalem, Israel. naomi.habib@mail.huji.ac.il.
³⁰ Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, USA. genevieve.konopka@utsouthwestern.edu.
³¹ Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA. genevieve.konopka@utsouthwestern.edu.
³² Neuroscience Institute, NYU Grossman School of Medicine, New York, NY, USA. shane.liddelow@nyulangone.org.
³³ Department of Neuroscience and Physiology, NYU Grossman School of Medicine, New York, NY, USA. shane.liddelow@nyulangone.org.
³⁴ Parekh Center for Interdisciplinary Neurology, NYU Grossman School of Medicine, New York, NY, USA. shane.liddelow@nyulangone.org.
³⁵ Department of Ophthalmology, NYU Grossman School of Medicine, New York, NY, USA. shane.liddelow@nyulangone.org.
³⁶ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA. tomasz.nowakowski@ucsf.edu.
³⁷ Department of Anatomy, University of California San Francisco, San Francisco, CA, USA. tomasz.nowakowski@ucsf.edu.
³⁸ Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA. tomasz.nowakowski@ucsf.edu.
³⁹ Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA. tomasz.nowakowski@ucsf.edu.
⁴⁰ The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA. tomasz.nowakowski@ucsf.edu.

PMID: 39627588
PMCID: PMC11949301 (available on 2025-12-03)
DOI: 10.1038/s41593-024-01827-9

Abstract

Single-cell and single-nucleus genomic approaches can provide unbiased and multimodal insights. Here, we discuss what constitutes a molecular cell atlas and how to leverage single-cell omics data to generate hypotheses and gain insights into cell transitions in development and disease of the nervous system. We share points of reflection on what to consider during study design and implementation as well as limitations and pitfalls.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

1. Ecker JR et al. The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas. Neuron 96, 542–557 (2017). 10.1016/j.neuron.2017.10.007 - DOI - PMC - PubMed
1. Zeisel A et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347, 1138–1142 (2015). 10.1126/science.aaa1934 - DOI - PubMed
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Applying single-cell and single-nucleus genomics to studies of cellular heterogeneity and cell fate transitions in the nervous system

Affiliations

Applying single-cell and single-nucleus genomics to studies of cellular heterogeneity and cell fate transitions in the nervous system

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources