Mapping microglia states in the human brain through the integration of high-dimensional techniques
Authors: Dieter Henrik Heiland
Marco Prinz
Josef Priller
Chotima Böttcher
Laufey Geirsdottir
Dominic Grün
Sagar
Tamara Seredenina
Takahiro Masuda
Christian Scheiwe
Roman Sankowski
Mukesch Johannes Shah
Elena Sindram
Andreas Muhs
Oliver Schnell
Journal: Nature Neuroscience (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Microglia; CNS; immune responses; neurological diseases; psychiatric diseases
Affiliations: Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany., Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany., AC Immune, Lausanne, Switzerland., Department of Neurosurgery, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany. ., Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg im Breisgau, Germany. ., Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany. ., DZNE and BIH, Berlin, Germany. ., University of Edinburgh and UK DRI, Edinburgh, UK. ., Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. ., Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany. .

Abstract:  Microglia are tissue-resident macrophages of the CNS that orchestrate local immune responses and contribute to several neurological and psychiatric diseases. Little is known about human microglia and how they orchestrate their highly plastic, context-specific adaptive responses during pathology. Here we combined two high-dimensional technologies, single-cell RNA-sequencing and time-of-flight mass cytometry, to identify microglia states in the human brain during homeostasis and disease. This approach enabled us to identify and characterize a previously unappreciated spectrum of transcriptional states in human microglia. These transcriptional states are determined by their spatial distribution, and they further change with aging and brain tumor pathology. This description of multiple microglia phenotypes in the human CNS may open promising new avenues for subset-specific therapeutic interventions. 

Retracted: No

PubPeer comments:
 ![file] image is duplicated in the control and GBM sample. , 
 ![file] here is the second duplicate image. :-( , 
 #2 S.A.: Using an image comparison tool, here are annotated Figures 3a, 5a, and Extended Data Figure 1A and 1b. Please note that there may be false positives (images marked as identical which are not) and some marked as repeated may be intentional by the authors. I thought you might find this useful in your analysis. *** ![file] *** ![file] *** ![file] *** ![file] , 
 #2 to help locate the issues, the Tmem119 and iba1 images are in Figures 5 and supplementary Figure 4, respectively. , 
 Thanks a lot for alerting us. We will carefully examine these unexpected issues. Best regards , 
 Author Correction: Mapping microglia states in the human brain through the integration of high-dimensional techniques https: www.nature.com articles s41593-022-01089-3 In the version of this article initially published, Fig.3b,c, Fig. 5au2013d, Extended Data Fig. 1 and Supplementary Fig. 8b contained errors. Fig. 3b and c showed incorrect immunohistochemistry quantifications. Fig. 5a contained a duplicate image for the TMEM119 control sample, and panels b and c showed incorrect immunohistochemistry quantifications. Fig. 5d contained an incorrect image for the t-SNE map of P2RY12; it was a duplicate of the map for HLA-DRA. Extended Data Fig. 1 contained incorrect images in panel a for Pat 7 (TMEM119), Pat 12 (TMEM119, CD74) and Pat 15 (CD68) and in panel b for Pat 3 (GFAP), Pat 12 (TMEM119 and P2YR12) and Pat 13 (TMEM119). Supplementary Fig. 8b contained an incorrect image for the CSF2 t-SNE panel. In addition, the legend for Fig. 5b as well as the description of Fig. 1b in Methods incorrectly said that the test used was a paired t-test; it should read u2018unpaired t-testu2019 in both places. In the Results section, the sentence u201cNormalization for the number of IBA1+ cells revealed lower expression of the bona fide microglial markers P2RY12 and TMEM119, and higher expression of HLA-DR (Fig. 5c)u201d should read u201cno change of expressionu201d instead of u201clower expressionu201d. The errors have been corrected in the HTML and PDF versions of the article. ,