Cecilia Lindskog – A spatio-temporal single-cell type map of human tissues
The aim of the research in my group is to utilize transcriptomics, large scale antibody-based proteomics, data integration and machine learning to generate a high-resolution spatio-temporal map of human tissues at the single cell type level.
During the last two decades, several large-scale efforts have been performed to map the biology of humans at different levels, including the mapping of all genes and proteins encoded within the human genome. However, the continuous emergence of new or upgraded technologies within the field of omics enable analysis with an ever increasing width and depth. Analysis of gene expression has gone from studies at the level of organs and tissues to distinguishing differences between single cells.
In our research we employ a multiomics systems biology approach, integrating different omics methods to study the spatio-temporal expression of proteins. We mainly utilize RNA sequencing data in combination with antibody-based imaging techniques to map the expression of proteins. One of the benefits with antibody-based proteomics is the possibility to localize proteins in their natural environment in intact tissue sections, making it possible to distinguish the spatial distribution of a protein in different cell types or subcellular structures.
Our lab has established a multiplex immunostaining method based on fluorescently labeled antibodies that enables simultaneous staining of six proteins in the same tissue section. Analyzing the co-localization between an unknown protein and five known cell type-specific markers makes it possible to study the expression of proteins within hard-to-distinguish cell types and novel cell states. Although we are involved in the exploration of protein expression in tissues across the entire human body, the main focus of our research is on healthy reproductive organs and cancers within the ovary and prostate.
Our research group is also affiliated with the Human Protein Atlas (HPA) project, initiated in 2003 with the aim to map all human proteins in tissues, cells and blood, both in health and disease. The HPA project is a collaboration between Uppsala University, Royal Institute of Technology and Karolinska Institute, and the open-access database (www.proteinatlas.org) has grown to become one of the world’s largest biological online resources. Our research group contributes with the profiling of human genes and proteins in healthy and diseased tissues, mainly utilizing antibody-based proteomics integrated with transcriptomics at the tissue and single-cell type level.
Read more about our research and the HPA project
Methods for tissue profiling in the Human Protein Atlas project
Group members
Publications
A human stomach cell type transcriptome atlas
Part of BMC Biology, 2024
- DOI for A human stomach cell type transcriptome atlas
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CD93 maintains endothelial barrier function and limits metastatic dissemination
Part of JCI Insight, 2024
- DOI for CD93 maintains endothelial barrier function and limits metastatic dissemination
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Deubiquitinase USP9x regulates the proline biosynthesis pathway in non-small cell lung cancer
Part of Cell Death Discovery, 2024
- DOI for Deubiquitinase USP9x regulates the proline biosynthesis pathway in non-small cell lung cancer
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Part of Human Reproduction Open, 2024
- DOI for Effects of chemical in vitro activation versus fragmentation on human ovarian tissue and follicle growth in culture
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Part of Toxicology, p. 153815, 2024
Part of Journal of Thoracic Oncology, 2024
Part of Nature Communications, 2024
- DOI for In-depth analysis of transcriptomes in ovarian cortical follicles from children and adults reveals interfollicular heterogeneity
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Persistent organic pollutants dysregulate energy homeostasis in human ovaries in vitro
Part of Environment International, 2024
- DOI for Persistent organic pollutants dysregulate energy homeostasis in human ovaries in vitro
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Stem cell-associated transcription factors in non-functioning pituitary neuroendocrine tumours.
Part of Free neuropathology, 2024
The 2023 Report on the Proteome from the HUPO Human Proteome Project
Part of Journal of Proteome Research, p. 532-549, 2024
The 2024 Report on the Human Proteome from the HUPO Human Proteome Project
Part of Journal of Proteome Research, p. 5296-5311, 2024
Part of Journal of Clinical Medicine, 2024
- DOI for The Human Phospholipase B-II Precursor (HPLBII-P) in Urine as a Novel Biomarker of Glomerular Activity in COVID-19 and Diabetes Mellitus
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Part of Journal of Clinical Medicine, 2024
- DOI for The Human Phospholipase B-II Precursor (HPLBII-P) in Urine as a Novel Biomarker of Increased Glomerular Production or Permeability in Diabetes Mellitus?
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Part of Journal of the Endocrine Society, 2024
- DOI for Transcriptome Analysis Reveals Distinct Patterns Between the Invasive and Noninvasive Pituitary Neuroendocrine Tumors
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Part of Journal of Proteome Research, p. 238-248, 2024
- DOI for Transcriptomics and Spatial Proteomics for Discovery and Validation of Missing Proteins in the Human Ovary
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Part of Microbiology Spectrum, 2023
- DOI for A Comparison of Host Responses to Infection with Wild-Type Avian Influenza Viruses in Chickens and Tufted Ducks
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Part of The Journal of General Physiology, 2023
Expression of cancer-testis antigens in the immune microenvironment of non-small cell lung cancer
Part of Molecular Oncology, p. 2603-2617, 2023
- DOI for Expression of cancer-testis antigens in the immune microenvironment of non-small cell lung cancer
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Part of Biomolecules, 2023
- DOI for Expression of IDO1 and PD-L2 in Patients with Benign Lymphadenopathies and Association with Autoimmune Diseases
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Part of Journal of Experimental & Clinical Cancer Research, 2023
- DOI for Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth
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Meningioma classification by immunohistochemistry: A replicability study
Part of BRAIN AND SPINE, 2023
- DOI for Meningioma classification by immunohistochemistry: A replicability study
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Part of Leukemia, p. 550-559, 2023
- DOI for Proteogenomic analysis of acute myeloid leukemia associates relapsed disease with reprogrammed energy metabolism both in adults and children
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Part of Nature Communications, 2023
- DOI for Segmenting functional tissue units across human organs using community-driven development of generalizable machine learning algorithms
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Part of Cancers, 2023
- DOI for Sex- and Female Age-Dependent Differences in Gene Expression in Diffuse Large B-Cell Lymphoma-Possible Estrogen Effects
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Spatial Proteomics for Further Exploration of Missing Proteins: A Case Study of the Ovary
Part of Journal of Proteome Research, p. 1071-1079, 2023
- DOI for Spatial Proteomics for Further Exploration of Missing Proteins: A Case Study of the Ovary
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The 2022 Report on the Human Proteome from the HUPO Human Proteome Project
Part of Journal of Proteome Research, p. 1024-1042, 2023
Part of PLOS ONE, 2023
- DOI for The clinical value of proneural, classical and mesenchymal protein signatures in WHO 2021 adult-type diffuse lower-grade gliomas
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The human protein atlas-Integrated omics for single cell mapping of the human proteome
Part of Protein Science, 2023
- DOI for The human protein atlas-Integrated omics for single cell mapping of the human proteome
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A human adipose tissue cell-type transcriptome atlas
Part of Cell Reports, 2022
- DOI for A human adipose tissue cell-type transcriptome atlas
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Part of Clinical and Translational Gastroenterology, 2022
Part of Nature Communications, 2022
- DOI for Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level
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Part of Nature Communications, 2022
- DOI for Estimating diagnostic uncertainty in artificial intelligence assisted pathology using conformal prediction
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Genome-wide annotation of protein-coding genes in pig
Part of BMC Biology, 2022
- DOI for Genome-wide annotation of protein-coding genes in pig
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Part of Frontiers in Immunology, 2022
- DOI for Genomic Multiple Sclerosis Risk Variants Modulate the Expression of the ANKRD55-IL6ST Gene Region in Immature Dendritic Cells
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Outcome in PCNSL patients and its association with PD-L1+leukocytes in the tumor microenvironment
Part of Acta Oncologica, p. 824-829, 2022
Protein Expression Profile of ACE2 in the Normal and COVID-19-Affected Human Brain.
Part of Journal of Proteome Research, p. 2137-2145, 2022
- DOI for Protein Expression Profile of ACE2 in the Normal and COVID-19-Affected Human Brain.
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Part of Neuro-Oncology Advances, 2022
- DOI for Stemness and clinical features in relation to the subventricular zone in diffuse lower-grade glioma: an exploratory study
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A Diffusion-like Process Accommodates New Crypts During Clonal Expansion in Human Colonic Epithelium
Part of Gastroenterology, p. 548-559, 2021
- DOI for A Diffusion-like Process Accommodates New Crypts During Clonal Expansion in Human Colonic Epithelium
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A single-cell type transcriptomics map of human tissues
Part of Science Advances, 2021
- DOI for A single-cell type transcriptomics map of human tissues
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Combined RNA/tissue profiling identifies novel Cancer/testis genes
Part of Molecular Oncology, p. 3003-3023, 2021
- DOI for Combined RNA/tissue profiling identifies novel Cancer/testis genes
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Part of Molecular & Cellular Proteomics, 2021
- DOI for DeepHistoClass: A Novel Strategy for Confident Classification of Immunohistochemistry Images Using Deep Learning
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Part of Journal of Pathology, p. 243-256, 2021
- DOI for Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
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Interobserver reproducibility of perineural invasion of prostatic adenocarcinoma in needle biopsies
Part of Virchows Archiv, p. 1109-1116, 2021
- DOI for Interobserver reproducibility of perineural invasion of prostatic adenocarcinoma in needle biopsies
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Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
Part of Nature Genetics, p. 1698, 2021
- DOI for Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
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Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CL(pro) substrate degradome
Part of Cell Reports, 2021
- DOI for Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CL(pro) substrate degradome
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Part of Acta Oncologica, p. 531-538, 2021
- DOI for PD-L1 and IDO1 are potential targets for treatment in patients with primary diffuse large B-cell lymphoma of the CNS
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Part of Journal of Proteome Research, p. 5227-5240, 2021
Spatiotemporal dissection of the cell cycle with single-cell proteogenomics
Part of Nature, p. 649-654, 2021
The Human Protein Atlas - Spatial localization of the human proteome in health and disease
Part of Protein Science, p. 218-233, 2021
Part of EBioMedicine, 2021
- DOI for The prognostic impact of the tumour stroma fraction: A machine learning-based analysis in 16 human solid tumour types
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A high-stringency blueprint of the human proteome
Part of Nature Communications, 2020
- DOI for A high-stringency blueprint of the human proteome
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An atlas of the protein-coding genes in the human, pig, and mouse brain
Part of Science, p. 1090-+, 2020
Part of The Lancet Oncology, p. 222-232, 2020
Part of Cancer Letters, p. 121-132, 2020
Candidate protein biomarkers in pancreatic neuroendocrine neoplasms grade 3
Part of Scientific Reports, 2020
- DOI for Candidate protein biomarkers in pancreatic neuroendocrine neoplasms grade 3
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Enhanced Validation of Antibodies Enables the Discovery of Missing Proteins
Part of Journal of Proteome Research, p. 4766-4781, 2020
- DOI for Enhanced Validation of Antibodies Enables the Discovery of Missing Proteins
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Marginal zone lymphoma expression of histidine-rich glycoprotein correlates with improved survival
Part of eJHaem, p. 199-207, 2020
Part of Journal of Pathology, p. 387-396, 2020
- DOI for Perivascular Neuropilin-1 expression is an independent marker of improved survival in renal cell carcinoma
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Proximity Ligation Assay as a Tool for Antibody Validation in Human Tissues
Part of Journal of Histochemistry and Cytochemistry, p. 515-529, 2020
Part of Journal of Proteome Research, p. 4735-4746, 2020
Somatostatin receptor expression and mTOR pathway activation in glioneuronal tumours of childhood
Part of Seizure, p. 123-130, 2020
Part of British Journal of Cancer, p. 1164-1177, 2020
Part of Cancers, 2020
The Dynamic Transcriptional Cell Atlas of Testis Development during Human Puberty
Part of Cell Stem Cell, p. 262-+, 2020
- DOI for The Dynamic Transcriptional Cell Atlas of Testis Development during Human Puberty
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The protein expression profile of ACE2 in human tissues
Part of Molecular Systems Biology, 2020
Tumor endothelial ELTD1 as a predictive marker for treatment of renal cancer patients with sunitinib
Part of BMC Cancer, 2020
- DOI for Tumor endothelial ELTD1 as a predictive marker for treatment of renal cancer patients with sunitinib
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A genome-wide transcriptomic analysis of protein-coding genes in human blood cells
Part of Science, p. 1471-+, 2019
Part of Molecular & Cellular Proteomics, p. 461-476, 2019
Part of Frontiers in Microbiology, 2019
- DOI for Attachment Patterns of Human and Avian Influenza Viruses to Trachea and Colon of 26 Bird Species: Support for the Community Concept
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Part of Journal of Proteome Research, p. 4215-4230, 2019
Part of Oncogenesis, 2019
- DOI for PPP2R2A prostate cancer haploinsufficiency is associated with worse prognosis and a high vulnerability to B55 alpha/PP2A reconstitution that triggers centrosome destabilization
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Part of Journal of Thoracic Oncology, p. 628-640, 2019
- DOI for Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC
- Download full text (pdf) of Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC
Part of Clinical Lung Cancer, p. 258-2620, 2019
Part of Science Signaling, 2019
Part of Journal of Cancer, p. 3224-3231, 2019
- DOI for Tumoral pyruvate kinase L/R as a predictive marker for the treatment of renal cancer patients with sunitinib and sorafenib
- Download full text (pdf) of Tumoral pyruvate kinase L/R as a predictive marker for the treatment of renal cancer patients with sunitinib and sorafenib
Part of Journal of Thoracic Oncology, p. 1676-1691, 2018
Characterization of avian influenza virus attachment patterns to human and pig tissues
Part of Scientific Reports, 2018
- DOI for Characterization of avian influenza virus attachment patterns to human and pig tissues
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Part of Journal of Biological Chemistry, p. 18477-18493, 2018
Enhanced validation of antibodies for research applications
Part of Nature Communications, 2018
- DOI for Enhanced validation of antibodies for research applications
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Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium
Part of Cell Stem Cell, p. 909-91800000000, 2018
- DOI for Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium
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Part of Journal of Proteome Research, p. 4127-4137, 2018
The adult human testis transcriptional cell atlas
Part of Cell Research, p. 1141-1157, 2018
- DOI for The adult human testis transcriptional cell atlas
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The human protein atlas: A spatial map of the human proteome
Part of Protein Science, p. 233-244, 2018
Part of Journal of Pathology, p. 311-322, 2018
- DOI for VEGF receptor-2/neuropilin 1 trans-complex formation between endothelial and tumor cells is an independent predictor of pancreatic cancer survival
- Download full text (pdf) of VEGF receptor-2/neuropilin 1 trans-complex formation between endothelial and tumor cells is an independent predictor of pancreatic cancer survival
A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family
Part of Nature Communications, 2017
- DOI for A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family
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A pathology atlas of the human cancer transcriptome
Part of Science, 2017
Part of Acta Neuropathologica, p. 675-677, 2017
A subcellular map of the human proteome
Part of Science, 2017
Part of Cell Stem Cell, p. 533-546, 2017
Part of Journal of Proteome Research, p. 4340-4351, 2017
A Systematic Characterization of Aquaporin-9 Expression in Human Normal and Pathological Tissues
Part of Journal of Histochemistry and Cytochemistry, p. 287-300, 2016
Looking for Missing Proteins in the Proteome of Human Spermatozoa: An Update
Part of Journal of Proteome Research, p. 3998-4019, 2016
Profiling cancer testis antigens in non-small-cell lung cancer
Part of JCI INSIGHT, 2016
Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma
Part of Allergy. European Journal of Allergy and Clinical Immunology, p. 1357-1361, 2016
Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma
Part of Allergy. European Journal of Allergy and Clinical Immunology, p. 1357-1361, 2016
Part of PLOS ONE, 2016
- DOI for Serum Autoantibody Profiling of Patients with Paraneoplastic and Non-Paraneoplastic Autoimmune Retinopathy
- Download full text (pdf) of Serum Autoantibody Profiling of Patients with Paraneoplastic and Non-Paraneoplastic Autoimmune Retinopathy
Part of PLOS ONE, 2016
System-wide Clinical Proteomics of Breast Cancer Reveals Global Remodeling of Tissue Homeostasis
Part of CELL SYSTEMS, p. 172-184, 2016
The Human Protein Atlas – an important resource for basic and clinical research
Part of Expert Review of Proteomics, p. 627-629, 2016
The Human Protein Atlas: an important resource for basic and clinical research
Part of Expert Review of Proteomics, p. 627-629, 2016