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Habets, Philippe C. (author), Kalafatakis, Konstantinos (author), Dzyubachyk, O. (author), van der Werff, Steven J.A. (author), Keo, D.L. (author), Thakrar, Jamini (author), Mahfouz, A.M.E.T.A. (author), Pereira, Alberto M. (author), Russell, Georgina M. (author)The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and...journal article 2023
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Ferraro, F. (author), Fevga, Christina (author), Bonifati, Vincenzo (author), Mandemakers, Wim (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)Several studies have analyzed gene expression profiles in the substantia nigra to better understand the pathological mechanisms causing Parkinson’s disease (PD). However, the concordance between the identified gene signatures in these individual studies was generally low. This might have been caused by a change in cell type composition as loss...journal article 2022
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Wang, Gangqi (author), Heijs, Bram (author), Kostidis, Sarantos (author), Mahfouz, A.M.E.T.A. (author), Rietjens, Rosalie G.J. (author), Bijkerk, Roel (author), Koudijs, Angela (author), van der Pluijm, Loïs A.K. (author), van den Berg, Cathelijne W. (author)A common drawback of metabolic analyses of complex biological samples is the inability to consider cell-to-cell heterogeneity in the context of an organ or tissue. To overcome this limitation, we present an advanced high-spatial-resolution metabolomics approach using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI...journal article 2022
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Wang, Gangqi (author), Heijs, Bram (author), Kostidis, Sarantos (author), Rietjens, Rosalie G.J. (author), Mahfouz, A.M.E.T.A. (author), Chuva de Sousa Lopes, Susana M. (author), van den Berg, Cathelijne W. (author), van den Berg, Bernard M. (author), Rabelink, Ton J. (author)Accumulating evidence demonstrates important roles for metabolism in cell fate determination. However, it is a challenge to assess metabolism at a spatial resolution that acknowledges both heterogeneity and cellular dynamics in its tissue microenvironment. Using a multi-omics platform to study cell-type-specific dynamics in metabolism in...journal article 2022
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Morgana, Florencia (author), Opstelten, Rianne (author), Slot, Manon C. (author), Scott, Andrew M. (author), van Lier, René A.W. (author), Blom, Bianca (author), Mahfouz, A.M.E.T.A. (author), Amsen, Derk (author)CD4+CD25+FOXP3+ regulatory T (Treg) cells control immunological tolerance. Treg cells are generated in the thymus (tTreg) or in the periphery. Their superior lineage fidelity makes tTregs the preferred cell type for adoptive cell therapy (ACT). How human tTreg cells develop is incompletely understood. By combining single-cell transcriptomics...journal article 2022
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Bourgonje, Arno R. (author), Hu, Shixian (author), Spekhorst, Lieke M. (author), Zhernakova, Daria V. (author), Vila, Arnau Vich (author), Li, Yanni (author), Charrout, M. (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)Background and Aims: Protein profiling in patients with inflammatory bowel diseases [IBD] for diagnostic and therapeutic purposes is underexplored. This study analysed the association between phenotype, genotype, and the plasma proteome in IBD. Methods: A total of 92 inflammation-related proteins were quantified in plasma of 1028 patients...journal article 2022
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Dieckman, Tessa (author), Schreurs, Mette (author), Mahfouz, A.M.E.T.A. (author), Kooy-Winkelaar, Yvonne (author), Neefjes-Borst, Andra (author), Bouma, Gerd (author), Koning, Frits (author)Background & Aims: Refractory celiac disease type II (RCDII) is a rare indolent lymphoma in the small intestine characterized by a clonally expanded intraepithelial intracellular CD3<sup>+</sup>surfaceCD3<sup>-</sup>CD7<sup>+</sup>CD56<sup>-</sup> aberrant cell population. However, RCDII pathogenesis is ill-defined. Here, we aimed at...journal article 2022
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van Unen, Vincent (author), Ouboter, Laura F. (author), Li, Na (author), Schreurs, Mette (author), Abdelaal, T.R.M. (author), Kooy-Winkelaar, Yvonne (author), Beyrend, Guillaume (author), Höllt, T. (author), Maljaars, P. W.Jeroen (author), Mearin, M. Luisa (author), Mahfouz, A.M.E.T.A. (author), Witte, Anne M.C. (author), Clemens, Cornelis H.M. (author), Abraham, Sunje (author), Escher, Johanna C. (author), Lelieveldt, B.P.F. (author), Pascutti, M. Fernanda (author), van der Meulen – de Jong, Andrea E. (author), Koning, Frits (author)Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high...journal article 2022
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Eltager, M.A.M.E. (author), Abdelaal, T.R.M. (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)Motivation: Single-cell multi-omics assays simultaneously measure different molecular features from the same cell. A key question is how to benefit from the complementary data available and perform cross-modal clustering of cells. Results: We propose Single-Cell Multi-omics Clustering (scMoC), an approach to identify cell clusters from data...journal article 2022
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Vergoossen, Dana L.E. (author), Keo, D.L. (author), Mahfouz, A.M.E.T.A. (author), Huijbers, Maartje G. (author)Myasthenia gravis (MG) is an acquired autoimmune disorder caused by autoantibodies binding acetylcholine receptors (AChR), muscle-specific kinase (MuSK), agrin or low-density lipoprotein receptor-related protein 4 (Lrp4). These autoantibodies inhibit neuromuscular transmission by blocking the function of these proteins and thereby cause...journal article 2021
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Bauduin, S.E.E.C. (author), den Rooijen, I.L.B. (author), Meijer, M. (author), van der Werff, S.J.A. (author), Keo, D.L. (author), Dzyubachyk, O. (author), Pereira, A.M. (author), Giltay, E.J. (author), van der Wee, N.J.A. (author), Meijer, O.C. (author), Mahfouz, A.M.E.T.A. (author)Introduction: Cushing's disease (CD) is a rare and severe endocrine disease characterized by hypercortisolemia. Previous studies have found structural brain alterations in remitted CD patients compared to healthy controls, specifically in the anterior cingulate cortex (ACC). However, potential mechanisms through which these persistent...journal article 2021
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Transcriptomic Signatures Associated With Regional Cortical Thickness Changes in Parkinson’s DiseaseKeo, D.L. (author), Dzyubachyk, Oleh (author), Van Der Grond, Jeroen (author), van Hilten, Jacobus J. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)Cortical atrophy is a common manifestation in Parkinson’s disease (PD), particularly in advanced stages of the disease. To elucidate the molecular underpinnings of cortical thickness changes in PD, we performed an integrated analysis of brain-wide healthy transcriptomic data from the Allen Human Brain Atlas and patterns of cortical thickness...journal article 2021
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Groen, Nathalie (author), Leenders, Floris (author), Mahfouz, A.M.E.T.A. (author), Munoz-Garcia, Amadeo (author), Muraro, Mauro J. (author), de Graaf, Natascha (author), Rabelink, Ton J. (author), Hoeben, Rob (author), Reinders, M.J.T. (author)The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet...journal article 2021
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Viho, Eva M.G. (author), Buurstede, Jacobus C. (author), Berkhout, Jari B. (author), Mahfouz, A.M.E.T.A. (author), Meijer, Onno C. (author)Glucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent glucocorticoid target and expresses both the glucocorticoid receptor (GR: Nr3c1) and the mineralocorticoid receptor (MR: Nr3c2). These nuclear steroid receptors act as ligand-dependent...journal article 2021
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Coutinho de Almeida, Rodrigo (author), Mahfouz, A.M.E.T.A. (author), Mei, Hailiang (author), Houtman, Evelyn (author), den Hollander, Wouter (author), Soul, Jamie (author), Suchiman, Eka (author), Nelissen, R.G.H.H. (author), Reinders, M.J.T. (author)OBJECTIVE: To identify OA subtypes based on cartilage transcriptomic data in cartilage tissue and characterize their underlying pathophysiological processes and/or clinically relevant characteristics. METHODS: This study includes n = 66 primary OA patients (41 knees and 25 hips), who underwent a joint replacement surgery, from which...journal article 2021
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Meijer, Mandy (author), Keo, D.L. (author), van Leeuwen, Judith M.C. (author), Dzyubachyk, Oleh (author), Meijer, Onno C. (author), Vinkers, Christiaan H. (author), Mahfouz, A.M.E.T.A. (author)The biological mechanisms underlying inter-individual differences in human stress reactivity remain poorly understood. We aimed to identify the molecular underpinning of aberrant neural stress sensitivity in individuals at risk for schizophrenia. Linking mRNA expression data from the Allen Human Brain Atlas to task-based fMRI revealed 201...journal article 2021
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A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brainJoglekar, Anoushka (author), Prjibelski, Andreyi (author), Mahfouz, A.M.E.T.A. (author), Collier, Paul (author), Lin, Susan (author), Schlusche, Anna Katharina (author), Marrocco, Jordan (author), Williams, Stephen R. (author), Haase, Bettina (author)Splicing varies across brain regions, but the single-cell resolution of regional variation is unclear. We present a single-cell investigation of differential isoform expression (DIE) between brain regions using single-cell long-read sequencing in mouse hippocampus and prefrontal cortex in 45 cell types at postnatal day 7 (www.isoformAtlas.com...journal article 2021
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Keo, D.L. (author), Dzyubachyk, Oleh (author), van der Grond, Jeroen (author), Hafkemeijer, Anne (author), van de Berg, Wilma D.J. (author), van Hilten, Jacobus J. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)Structural covariance networks are able to identify functionally organized brain regions by gray matter volume covariance across a population. We examined the transcriptomic signature of such anatomical networks in the healthy brain using postmortem microarray data from the Allen Human Brain Atlas. A previous study revealed that a posterior...journal article 2021
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Yu, W. (author), Mahfouz, A.M.E.T.A. (author), Reinders, M.J.T. (author)The power of single-cell RNA sequencing (scRNA-seq) in detecting cell heterogeneity or developmental process is becoming more and more evident every day. The granularity of this knowledge is further propelled when combining two batches of scRNA-seq into a single large dataset. This strategy is however hampered by technical differences between...journal article 2021
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Michielsen, L.C.M. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)Supervised methods are increasingly used to identify cell populations in single-cell data. Yet, current methods are limited in their ability to learn from multiple datasets simultaneously, are hampered by the annotation of datasets at different resolutions, and do not preserve annotations when retrained on new datasets. The latter point is...journal article 2021