TY - JOUR
T1 - Distinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury
AU - Floriddia, Elisa M.
AU - Lourenço, Tânia
AU - Zhang, Shupei
AU - van Bruggen, David
AU - Hilscher, Markus M.
AU - Kukanja, Petra
AU - Gonçalves dos Santos, João P.
AU - Altınkök, Müge
AU - Yokota, Chika
AU - Llorens-Bobadilla, Enric
AU - Mulinyawe, Sara B.
AU - Grãos, Mário
AU - Sun, Lu O.
AU - Frisén, Jonas
AU - Nilsson, Mats
AU - Castelo-Branco, Gonçalo
N1 - Funding Information:
We would like to thank Sarah Foerster, Richa B. Tripathi, William D. Richardson, and Robin J.M. Franklin for the fruitful discussions and sharing the Emx1::Cre-Sox10::Cre-LoxP-GFP-STOP-TdTom line, Antonio del Sol and Srikanth Ravichandran for discussions, Rashid Holtinkoski, Eneritz Agirre, Ana Mendanha Falcão, Alessandra Nanni, Johnny Söderlund, Ahmad Moshref, Tony Jimenez-Baristain, Lesley Kirby, the Facility Management and Administration at Biomedicum (Karolinska Institutet, Stockholm) for laboratory management and support. Dr. Göran Månsson and Connla Edwards at the Biomedicum Imaging Core Facility (Karolinska Institutet, Stockholm), Dr. Jaromir Mikes at the Mass Cytometry National Facility (SciLife Lab, Stockholm); Drs. Karolina Wal-lenborg, Anna Juréus, Marcela Ferella at the Eukariotic Single Cell Genomics facility (SciLife Lab, Stockholm) “In situ sequencing” unit of the spatial-omics infrastructure (SciLifeLab, Stockholm), for technical assistance with the ISS experiments; Katarina Ericsson, Kristoffer Tenebro Berglund, Johanna Hornstrand at the Comparative Medicine Biomedicum facility (Karolinska Institutet, Stockholm) and their respective facility managements, the National Genomics Infrastructure and Uppmax for providing assistance in massive parallel sequencing and computational infrastructure. The bioinfor-matics computations were performed on resources provided by the Swedish National Infrastructure for Computing at UPPMAX, Uppsala University. NIH Pathway to Independent Award (5K99EY029330) supported L.O.S. T.L. was supported by a Ph.D. grant (SFRH/BD/114731/2016) and M.G. was supported by grant POCI-01-0145-FEDER-029516, cofinanced by the ERDF/FEDER under the framework Competitiveness and Internationalization Operational Program (POCI) and funds from FCT/‘Ministeŕ io da Ciencia,̂ Tecnologia e Ensino Superior’ (FCT/MCTES) through the Portuguese State Budget. Work in G.C.-B.’s research group was supported by Swedish Research Council (grant 2015-03558 and 2019-01360), European Union (Horizon 2020 Research and Innovation Programme/ European Research Council Consolidator Grant EPIScOPE, grant agreement number 681893), Swedish Brain Foundation (FO2017-0075), Knut and Alice Wallenberg Foundation (grant 2019-0107), The Swedish Society for Medical Research (SSMF, grant JUB2019), Ming Wai Lau Centre for Reparative Medicine, Strategic Research Programme in Neuroscience (StratNeuro) and Karolinska Institutet.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - Mature oligodendrocytes (MOLs) show transcriptional heterogeneity, the functional consequences of which are unclear. MOL heterogeneity might correlate with the local environment or their interactions with different neuron types. Here, we show that distinct MOL populations have spatial preference in the mammalian central nervous system (CNS). We found that MOL type 2 (MOL2) is enriched in the spinal cord when compared to the brain, while MOL types 5 and 6 (MOL5/6) increase their contribution to the OL lineage with age in all analyzed regions. MOL2 and MOL5/6 also have distinct spatial preference in the spinal cord regions where motor and sensory tracts run. OL progenitor cells (OPCs) are not specified into distinct MOL populations during development, excluding a major contribution of OPC intrinsic mechanisms determining MOL heterogeneity. In disease, MOL2 and MOL5/6 present different susceptibility during the chronic phase following traumatic spinal cord injury. Our results demonstrate that the distinct MOL populations have different spatial preference and different responses to disease.
AB - Mature oligodendrocytes (MOLs) show transcriptional heterogeneity, the functional consequences of which are unclear. MOL heterogeneity might correlate with the local environment or their interactions with different neuron types. Here, we show that distinct MOL populations have spatial preference in the mammalian central nervous system (CNS). We found that MOL type 2 (MOL2) is enriched in the spinal cord when compared to the brain, while MOL types 5 and 6 (MOL5/6) increase their contribution to the OL lineage with age in all analyzed regions. MOL2 and MOL5/6 also have distinct spatial preference in the spinal cord regions where motor and sensory tracts run. OL progenitor cells (OPCs) are not specified into distinct MOL populations during development, excluding a major contribution of OPC intrinsic mechanisms determining MOL heterogeneity. In disease, MOL2 and MOL5/6 present different susceptibility during the chronic phase following traumatic spinal cord injury. Our results demonstrate that the distinct MOL populations have different spatial preference and different responses to disease.
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U2 - 10.1038/s41467-020-19453-x
DO - 10.1038/s41467-020-19453-x
M3 - Article
C2 - 33203872
AN - SCOPUS:85096091655
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 5860
ER -