Whole-body integration of gene expression and single-cell morphology

Hernando M. Vergara; Constantin Pape; Kimberly I. Meechan; Valentyna Zinchenko; Christel Genoud; Adrian A. Wanner; Kevin Nzumbi Mutemi; Benjamin Titze; Rachel M. Templin; Paola Y. Bertucci; Oleg Simakov; Wiebke Dürichen; Pedro Machado; Emily L. Savage; Lothar Schermelleh; Yannick Schwab; Rainer W. Friedrich; Anna Kreshuk; Christian Tischer; Detlev Arendt

doi:10.1016/j.cell.2021.07.017

Whole-body integration of gene expression and single-cell morphology

Hernando M. Vergara, Constantin Pape, Kimberly I. Meechan, Valentyna Zinchenko, Christel Genoud, Adrian A. Wanner, Kevin Nzumbi Mutemi, Benjamin Titze, Rachel M. Templin, Paola Y. Bertucci, Oleg Simakov, Wiebke Dürichen, Pedro Machado, Emily L. Savage, Lothar Schermelleh, Yannick Schwab^*, Rainer W. Friedrich, Anna Kreshuk, Christian Tischer, Detlev Arendt

^*Corresponding author for this work

Centre for Ultrastructural Imaging

Research output: Contribution to journal › Article › peer-review

40 Citations (Scopus)

Abstract

Animal bodies are composed of cell types with unique expression programs that implement their distinct locations, shapes, structures, and functions. Based on these properties, cell types assemble into specific tissues and organs. To systematically explore the link between cell-type-specific gene expression and morphology, we registered an expression atlas to a whole-body electron microscopy volume of the nereid Platynereis dumerilii. Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size. Clustering of segmented cells according to gene expression reveals spatially coherent tissues. In the brain, genetically defined groups of neurons match ganglionic nuclei with coherent projections. Besides interneurons, we uncover sensory-neurosecretory cells in the nereid mushroom bodies, which thus qualify as sensory organs. They furthermore resemble the vertebrate telencephalon by molecular anatomy. We provide an integrated browser as a Fiji plugin for remote exploration of all available multimodal datasets.

Original language	English
Pages (from-to)	4819-4837.e22
Journal	Cell
Volume	184
Issue number	18
DOIs	https://doi.org/10.1016/j.cell.2021.07.017
Publication status	Published - 2 Sept 2021

Keywords

automatic segmentation
cell types
gene expression atlas
image registration
machine learning
multimodal data integration
mushroom bodies
Platynereis dumerilii
telencephalon
volume electron microscopy

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10.1016/j.cell.2021.07.017

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Vergara, H. M., Pape, C., Meechan, K. I., Zinchenko, V., Genoud, C., Wanner, A. A., Mutemi, K. N., Titze, B., Templin, R. M., Bertucci, P. Y., Simakov, O., Dürichen, W., Machado, P., Savage, E. L., Schermelleh, L., Schwab, Y., Friedrich, R. W., Kreshuk, A., Tischer, C., & Arendt, D. (2021). Whole-body integration of gene expression and single-cell morphology. Cell, 184(18), 4819-4837.e22. https://doi.org/10.1016/j.cell.2021.07.017

@article{9f6a2753ffa5467690fba8b0b20c6988,

title = "Whole-body integration of gene expression and single-cell morphology",

abstract = "Animal bodies are composed of cell types with unique expression programs that implement their distinct locations, shapes, structures, and functions. Based on these properties, cell types assemble into specific tissues and organs. To systematically explore the link between cell-type-specific gene expression and morphology, we registered an expression atlas to a whole-body electron microscopy volume of the nereid Platynereis dumerilii. Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size. Clustering of segmented cells according to gene expression reveals spatially coherent tissues. In the brain, genetically defined groups of neurons match ganglionic nuclei with coherent projections. Besides interneurons, we uncover sensory-neurosecretory cells in the nereid mushroom bodies, which thus qualify as sensory organs. They furthermore resemble the vertebrate telencephalon by molecular anatomy. We provide an integrated browser as a Fiji plugin for remote exploration of all available multimodal datasets.",

keywords = "automatic segmentation, cell types, gene expression atlas, image registration, machine learning, multimodal data integration, mushroom bodies, Platynereis dumerilii, telencephalon, volume electron microscopy",

author = "Vergara, {Hernando M.} and Constantin Pape and Meechan, {Kimberly I.} and Valentyna Zinchenko and Christel Genoud and Wanner, {Adrian A.} and Mutemi, {Kevin Nzumbi} and Benjamin Titze and Templin, {Rachel M.} and Bertucci, {Paola Y.} and Oleg Simakov and Wiebke D{\"u}richen and Pedro Machado and Savage, {Emily L.} and Lothar Schermelleh and Yannick Schwab and Friedrich, {Rainer W.} and Anna Kreshuk and Christian Tischer and Detlev Arendt",

note = "Funding Information: We thank Josep Moscardo and EMBL IT Services for cloud infrastructure and Stephan Saalfeld, Igor Pisarev, and Tobias Pietzsch for software design. We thank Gemma Estrada Girona for help with Figures 4 and 7 and the graphical abstract and for the design of the MoBIE logo. We thank Julia Tran and Remmer Janssen for curating muscle and neuropil segmentation and supervising groundtruth annotation. We thank Giulia Mizzon for annotations and segmentation validation, David Puga for helping reconstruct the midline and neuronal tracing, and Julieta Acevedo for H3K36me3 stains. Thanks to Sian Culley for the name MoBIE. H.M.V. was supported by an EMBO LTF, K.N.M. by Horizon 2020 “EvoCELL” project 766053 , and D.A. and P.Y.B. by the Advanced grant “NeuralCellTypeEvo” 788921 of the European Commission . Funding Information: We thank Josep Moscardo and EMBL IT Services for cloud infrastructure and Stephan Saalfeld, Igor Pisarev, and Tobias Pietzsch for software design. We thank Gemma Estrada Girona for help with Figures 4 and 7 and the graphical abstract and for the design of the MoBIE logo. We thank Julia Tran and Remmer Janssen for curating muscle and neuropil segmentation and supervising groundtruth annotation. We thank Giulia Mizzon for annotations and segmentation validation, David Puga for helping reconstruct the midline and neuronal tracing, and Julieta Acevedo for H3K36me3 stains. Thanks to Sian Culley for the name MoBIE. H.M.V. was supported by an EMBO LTF, K.N.M. by Horizon 2020 ?EvoCELL? project 766053, and D.A. and P.Y.B. by the Advanced grant ?NeuralCellTypeEvo? 788921 of the European Commission. Conceptualization, A.K. C.T. D.A. H.M.V. and Y.S.; methodology, A.A.W. A.K. C.G. C.P. C.T. H.M.V. K.I.M. and V.Z.; software, A.A.W. B.T. C.P. C.T. H.M.V. K.I.M. and V.Z.; validation, C.P. C.T. D.A. H.M.V. K.I.M. P.M. P.Y.B. R.M.T. V.Z. and Y.S.; formal analysis, C.P. H.M.V. K.I.M. O.S. and V.Z.; investigation, B.T. C.G. E.L.S. H.M.V. K.N.M. L.S. O.S. P.M. P.Y.B. and W.D.; resources, A.K. C.P. C.T. H.M.V. K.I.M. and V.Z.; data curation, C.P. K.I.M. and V.Z.; writing ? original draft, A.K. C.P. C.T. D.A. H.M.V. K.I.M. R.M.T. V.Z. and Y.S.; writing ? review and editing, A.A.W. A.K. B.T. C.G. C.P. C.T. D.A. H.M.V. K.I.M. R.M.T. R.W.F. V.Z. L.S. and Y.S.; visualization, C.P. C.T. H.M.V. K.I.M. R.M.T. V.Z. and Y.S.; supervision, A.K. C.P. C.T. D.A. H.M.V. and Y.S.; project administration, D.A. and Y.S.; funding acquisition, A.K. D.A. R.W.F. and Y.S. A.A.W. is the founder and owner of ariadne.ai ag. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = sep,

day = "2",

doi = "10.1016/j.cell.2021.07.017",

language = "English",

volume = "184",

pages = "4819--4837.e22",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "18",

}

Vergara, HM, Pape, C, Meechan, KI, Zinchenko, V, Genoud, C, Wanner, AA, Mutemi, KN, Titze, B, Templin, RM, Bertucci, PY, Simakov, O, Dürichen, W, Machado, P, Savage, EL, Schermelleh, L, Schwab, Y, Friedrich, RW, Kreshuk, A, Tischer, C & Arendt, D 2021, 'Whole-body integration of gene expression and single-cell morphology', Cell, vol. 184, no. 18, pp. 4819-4837.e22. https://doi.org/10.1016/j.cell.2021.07.017

TY - JOUR

T1 - Whole-body integration of gene expression and single-cell morphology

AU - Vergara, Hernando M.

AU - Pape, Constantin

AU - Meechan, Kimberly I.

AU - Zinchenko, Valentyna

AU - Genoud, Christel

AU - Wanner, Adrian A.

AU - Mutemi, Kevin Nzumbi

AU - Titze, Benjamin

AU - Templin, Rachel M.

AU - Bertucci, Paola Y.

AU - Simakov, Oleg

AU - Dürichen, Wiebke

AU - Machado, Pedro

AU - Savage, Emily L.

AU - Schermelleh, Lothar

AU - Schwab, Yannick

AU - Friedrich, Rainer W.

AU - Kreshuk, Anna

AU - Tischer, Christian

AU - Arendt, Detlev

N1 - Funding Information: We thank Josep Moscardo and EMBL IT Services for cloud infrastructure and Stephan Saalfeld, Igor Pisarev, and Tobias Pietzsch for software design. We thank Gemma Estrada Girona for help with Figures 4 and 7 and the graphical abstract and for the design of the MoBIE logo. We thank Julia Tran and Remmer Janssen for curating muscle and neuropil segmentation and supervising groundtruth annotation. We thank Giulia Mizzon for annotations and segmentation validation, David Puga for helping reconstruct the midline and neuronal tracing, and Julieta Acevedo for H3K36me3 stains. Thanks to Sian Culley for the name MoBIE. H.M.V. was supported by an EMBO LTF, K.N.M. by Horizon 2020 “EvoCELL” project 766053 , and D.A. and P.Y.B. by the Advanced grant “NeuralCellTypeEvo” 788921 of the European Commission . Funding Information: We thank Josep Moscardo and EMBL IT Services for cloud infrastructure and Stephan Saalfeld, Igor Pisarev, and Tobias Pietzsch for software design. We thank Gemma Estrada Girona for help with Figures 4 and 7 and the graphical abstract and for the design of the MoBIE logo. We thank Julia Tran and Remmer Janssen for curating muscle and neuropil segmentation and supervising groundtruth annotation. We thank Giulia Mizzon for annotations and segmentation validation, David Puga for helping reconstruct the midline and neuronal tracing, and Julieta Acevedo for H3K36me3 stains. Thanks to Sian Culley for the name MoBIE. H.M.V. was supported by an EMBO LTF, K.N.M. by Horizon 2020 ?EvoCELL? project 766053, and D.A. and P.Y.B. by the Advanced grant ?NeuralCellTypeEvo? 788921 of the European Commission. Conceptualization, A.K. C.T. D.A. H.M.V. and Y.S.; methodology, A.A.W. A.K. C.G. C.P. C.T. H.M.V. K.I.M. and V.Z.; software, A.A.W. B.T. C.P. C.T. H.M.V. K.I.M. and V.Z.; validation, C.P. C.T. D.A. H.M.V. K.I.M. P.M. P.Y.B. R.M.T. V.Z. and Y.S.; formal analysis, C.P. H.M.V. K.I.M. O.S. and V.Z.; investigation, B.T. C.G. E.L.S. H.M.V. K.N.M. L.S. O.S. P.M. P.Y.B. and W.D.; resources, A.K. C.P. C.T. H.M.V. K.I.M. and V.Z.; data curation, C.P. K.I.M. and V.Z.; writing ? original draft, A.K. C.P. C.T. D.A. H.M.V. K.I.M. R.M.T. V.Z. and Y.S.; writing ? review and editing, A.A.W. A.K. B.T. C.G. C.P. C.T. D.A. H.M.V. K.I.M. R.M.T. R.W.F. V.Z. L.S. and Y.S.; visualization, C.P. C.T. H.M.V. K.I.M. R.M.T. V.Z. and Y.S.; supervision, A.K. C.P. C.T. D.A. H.M.V. and Y.S.; project administration, D.A. and Y.S.; funding acquisition, A.K. D.A. R.W.F. and Y.S. A.A.W. is the founder and owner of ariadne.ai ag. Publisher Copyright: © 2021 The Authors

PY - 2021/9/2

Y1 - 2021/9/2

N2 - Animal bodies are composed of cell types with unique expression programs that implement their distinct locations, shapes, structures, and functions. Based on these properties, cell types assemble into specific tissues and organs. To systematically explore the link between cell-type-specific gene expression and morphology, we registered an expression atlas to a whole-body electron microscopy volume of the nereid Platynereis dumerilii. Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size. Clustering of segmented cells according to gene expression reveals spatially coherent tissues. In the brain, genetically defined groups of neurons match ganglionic nuclei with coherent projections. Besides interneurons, we uncover sensory-neurosecretory cells in the nereid mushroom bodies, which thus qualify as sensory organs. They furthermore resemble the vertebrate telencephalon by molecular anatomy. We provide an integrated browser as a Fiji plugin for remote exploration of all available multimodal datasets.

AB - Animal bodies are composed of cell types with unique expression programs that implement their distinct locations, shapes, structures, and functions. Based on these properties, cell types assemble into specific tissues and organs. To systematically explore the link between cell-type-specific gene expression and morphology, we registered an expression atlas to a whole-body electron microscopy volume of the nereid Platynereis dumerilii. Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size. Clustering of segmented cells according to gene expression reveals spatially coherent tissues. In the brain, genetically defined groups of neurons match ganglionic nuclei with coherent projections. Besides interneurons, we uncover sensory-neurosecretory cells in the nereid mushroom bodies, which thus qualify as sensory organs. They furthermore resemble the vertebrate telencephalon by molecular anatomy. We provide an integrated browser as a Fiji plugin for remote exploration of all available multimodal datasets.

KW - automatic segmentation

KW - cell types

KW - gene expression atlas

KW - image registration

KW - machine learning

KW - multimodal data integration

KW - mushroom bodies

KW - Platynereis dumerilii

KW - telencephalon

KW - volume electron microscopy

UR - http://www.scopus.com/inward/record.url?scp=85114048411&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2021.07.017

DO - 10.1016/j.cell.2021.07.017

M3 - Article

C2 - 34380046

AN - SCOPUS:85114048411

SN - 0092-8674

VL - 184

SP - 4819-4837.e22

JO - Cell

JF - Cell

IS - 18

ER -

Whole-body integration of gene expression and single-cell morphology

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Keywords

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