Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease

Wei-Ting Chen; Ashley Lu; Katleen Craessaerts; Benjamin Pavie; Carlo Sala Frigerio; Nikky Corthout; Xiaoyan Qian; Jana Laláková; Malte Kühnemund; Iryna Voytyuk; Leen Wolfs; Renzo Mancuso; Evgenia Salta; Sriram Balusu; An Snellinx; Sebastian Munck; Aleksandra Jurek; Jose Fernandez Navarro; Takaomi C Saido; Inge Huitinga; Joakim Lundeberg; Mark Fiers; Bart De Strooper

doi:10.1016/j.cell.2020.06.038

Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease

Wei-Ting Chen, Ashley Lu, Katleen Craessaerts, Benjamin Pavie, Carlo Sala Frigerio, Nikky Corthout, Xiaoyan Qian, Jana Laláková, Malte Kühnemund, Iryna Voytyuk, Leen Wolfs, Renzo Mancuso, Evgenia Salta, Sriram Balusu, An Snellinx, Sebastian Munck, Aleksandra Jurek, Jose Fernandez Navarro, Takaomi C Saido, Inge HuitingaJoakim Lundeberg, Mark Fiers, Bart De Strooper

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Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.

Originele taal-2	Engels
Pagina's (van-tot)	976-991
Tijdschrift	Cell
Volume	182
DOI's	https://doi.org/10.1016/j.cell.2020.06.038
Status	Gepubliceerd - 2020

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10.1016/j.cell.2020.06.038

ST_manuscript_Chen et al_Cell_2020Accepted author manuscript, 556 KBLicentie: CC BY-NC-ND

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Chen, W-T., Lu, A., Craessaerts, K., Pavie, B., Sala Frigerio, C., Corthout, N., Qian, X., Laláková, J., Kühnemund, M., Voytyuk, I., Wolfs, L., Mancuso, R., Salta, E., Balusu, S., Snellinx, A., Munck, S., Jurek, A., Fernandez Navarro, J., Saido, T. C., ... De Strooper, B. (2020). Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease. Cell, 182, 976-991. https://doi.org/10.1016/j.cell.2020.06.038

Chen, Wei-Ting ; Lu, Ashley ; Craessaerts, Katleen ; Pavie, Benjamin ; Sala Frigerio, Carlo ; Corthout, Nikky ; Qian, Xiaoyan ; Laláková, Jana ; Kühnemund, Malte ; Voytyuk, Iryna ; Wolfs, Leen ; Mancuso, Renzo ; Salta, Evgenia ; Balusu, Sriram ; Snellinx, An ; Munck, Sebastian ; Jurek, Aleksandra ; Fernandez Navarro, Jose ; Saido, Takaomi C ; Huitinga, Inge ; Lundeberg, Joakim ; Fiers, Mark ; De Strooper, Bart. / Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease. In: Cell. 2020 ; Vol. 182. blz. 976-991.

@article{6ed482a17c04436eb493e7e4e21aaecd,

title = "Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease",

abstract = "Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.",

author = "Wei-Ting Chen and Ashley Lu and Katleen Craessaerts and Benjamin Pavie and {Sala Frigerio}, Carlo and Nikky Corthout and Xiaoyan Qian and Jana Lal{\'a}kov{\'a} and Malte K{\"u}hnemund and Iryna Voytyuk and Leen Wolfs and Renzo Mancuso and Evgenia Salta and Sriram Balusu and An Snellinx and Sebastian Munck and Aleksandra Jurek and {Fernandez Navarro}, Jose and Saido, {Takaomi C} and Inge Huitinga and Joakim Lundeberg and Mark Fiers and {De Strooper}, Bart",

year = "2020",

doi = "10.1016/j.cell.2020.06.038",

language = "English",

volume = "182",

pages = "976--991",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

}

Chen, W-T, Lu, A, Craessaerts, K, Pavie, B, Sala Frigerio, C, Corthout, N, Qian, X, Laláková, J, Kühnemund, M, Voytyuk, I, Wolfs, L, Mancuso, R, Salta, E, Balusu, S, Snellinx, A, Munck, S, Jurek, A, Fernandez Navarro, J, Saido, TC, Huitinga, I, Lundeberg, J, Fiers, M & De Strooper, B 2020, 'Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease', Cell, vol. 182, blz. 976-991. https://doi.org/10.1016/j.cell.2020.06.038

Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease. / Chen, Wei-Ting; Lu, Ashley; Craessaerts, Katleen; Pavie, Benjamin; Sala Frigerio, Carlo; Corthout, Nikky; Qian, Xiaoyan; Laláková, Jana; Kühnemund, Malte; Voytyuk, Iryna; Wolfs, Leen; Mancuso, Renzo; Salta, Evgenia; Balusu, Sriram; Snellinx, An; Munck, Sebastian; Jurek, Aleksandra; Fernandez Navarro, Jose; Saido, Takaomi C; Huitinga, Inge; Lundeberg, Joakim; Fiers, Mark; De Strooper, Bart.

In: Cell, Vol. 182, 2020, blz. 976-991.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

TY - JOUR

T1 - Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease

AU - Chen, Wei-Ting

AU - Lu, Ashley

AU - Craessaerts, Katleen

AU - Pavie, Benjamin

AU - Sala Frigerio, Carlo

AU - Corthout, Nikky

AU - Qian, Xiaoyan

AU - Laláková, Jana

AU - Kühnemund, Malte

AU - Voytyuk, Iryna

AU - Wolfs, Leen

AU - Mancuso, Renzo

AU - Salta, Evgenia

AU - Balusu, Sriram

AU - Snellinx, An

AU - Munck, Sebastian

AU - Jurek, Aleksandra

AU - Fernandez Navarro, Jose

AU - Saido, Takaomi C

AU - Huitinga, Inge

AU - Lundeberg, Joakim

AU - Fiers, Mark

AU - De Strooper, Bart

PY - 2020

Y1 - 2020

N2 - Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.

AB - Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.

U2 - 10.1016/j.cell.2020.06.038

DO - 10.1016/j.cell.2020.06.038

M3 - Article

C2 - 32702314

VL - 182

SP - 976

EP - 991

JO - Cell

JF - Cell

SN - 0092-8674

ER -

Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease

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