scholarly journals Human and Mouse Transcriptome Profiling Identifies Cross-Species Homology in Pulmonary and Lymph Node Mononuclear Phagocytes

Author(s):  
Sonia M. Leach ◽  
Sophie L. Gibbings ◽  
Anita D. Tewari ◽  
Shaikh M. Atif ◽  
Brian Vestal ◽  
...  
Cell Reports ◽  
2020 ◽  
Vol 33 (5) ◽  
pp. 108337
Author(s):  
Sonia M. Leach ◽  
Sophie L. Gibbings ◽  
Anita D. Tewari ◽  
Shaikh M. Atif ◽  
Brian Vestal ◽  
...  

Author(s):  
Sonia M. Leach ◽  
Sophie L. Gibbings ◽  
Anita D. Tewari ◽  
Shaikh M. Atif ◽  
Brian Vestal ◽  
...  

SummaryThe mononuclear phagocyte (MP) system consists of macrophages, monocytes, and dendritic cells (DCs). MP subtypes play distinct functional roles in steady state and inflammatory conditions. Though murine MPs are well characterized, their pulmonary and lymph node (LN) human homologs remain poorly understood. To address this gap, we created a gene expression compendium across 15 distinct human and 9 distinct murine MPs from lung, LN, blood, and spleen. Human blood MPs and murine spleen MPs served as validation datasets, as the human-mouse MP homologs are relatively well-defined in these tissues. In-depth RNA sequencing identified corresponding human-mouse MP subtypes and determined marker genes shared and divergent across between species counterparts. Unexpectedly, at the gene expression level, only 13-23% of the top 1000 marker genes (i.e., genes not shared across species-specific MP subtypes) overlapped in corresponding human-mouse MP counterparts, indicating a need for caution when translating mouse studies to human gene targets and functions. Lastly, CD88 was useful in both species to distinguish macrophage and tissue monocytes from DCs. Our cross-species gene expression compendium serves as a resource for future translational studies to investigate beforehand whether pursuing specific MP subtypes, or genes will prove fruitful.


1979 ◽  
Vol 150 (6) ◽  
pp. 1410-1420 ◽  
Author(s):  
A K Bhan ◽  
A B Collins ◽  
E E Schneeberger ◽  
R T McCluskey

Lewis rats were given a single i.v. injection of soluble immune complexes containing human serum albumin (HSA) and rabbit anti-HSA antibodies, prepared in antigen excess. This resulted in localization of HSA and rabbit gamma globulin (RGG) in glomerular mesangial regions without producing definite histologic changes. 24 h after the injection of immune complexes, groups of these rats received lymph node cells or T-cell preparations from syngeneic donors sensitized to RGG, HSA, or ovalbumin; another group received no cells. All of these groups and a group of normal control rats were given injections of [3H]thymidine at 18, 27, and 44 h. The animals were killed 48 h after the time of cell transfer. In histologic sections, glomerular abnormalities were found only in some of the animals that had received immune complexes and lymph node cells or T-cell populations from donors sensitized to HSA or RGG; the lesions were characterized by focal and segmental increase in cells in mesangial regions. Autoradiographs revealed significantly greater numbers of labeled cells in mesangial regions and glomerular capillaries in the groups that had received immune complexes and cells from HSA- or RGG-sensitized donors than in any of the other groups. Electronmicroscopic studies suggested that the increase in cellularity in mesangial regions resulted from an influx of mononuclear phagocytes. The findings indicate that cell-mediated reactions can be initiated by the interaction between sensitized T lymphocytes and antigens present in immune complexes within mesangial regions.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Chiara M Eandi ◽  
Hugo Charles Messance ◽  
Sébastien Augustin ◽  
Elisa Dominguez ◽  
Sophie Lavalette ◽  
...  

Photo-transduction in cone segments (CS) is crucial for high acuity daytime vision. For ill-defined reasons, CS degenerate in retinitis pigmentosa (RP) and in the transitional zone (TZ) of atrophic zones (AZ), which characterize geographic atrophy (GA). Our experiments confirm the loss of cone segments (CS) in the TZ of patients with GA and show their association with subretinal CD14+mononuclear phagocyte (MP) infiltration that is also reported in RP. Using human and mouse MPs in vitro and inflammation-prone Cx3cr1GFP/GFP mice in vivo, we demonstrate that MP-derived IL-1β leads to severe CS degeneration. Our results strongly suggest that subretinal MP accumulation participates in the observed pathological photoreceptor changes in these diseases. Inhibiting subretinal MP accumulation or Il-1β might protect the CS and help preserve high acuity daytime vision in conditions characterized by subretinal inflammation, such as AMD and RP.


1983 ◽  
Vol 158 (1) ◽  
pp. 126-145 ◽  
Author(s):  
W C Van Voorhis ◽  
R M Steinman ◽  
L S Hair ◽  
J Luban ◽  
M D Witmer ◽  
...  

3C10 and 1D9 are two related monoclonal antibodies that specifically identify human mononuclear phagocytes in a large number of sites, including blood monocytes, alveolar macrophages, and macrophages in tissue sections of spleen, lymph node, and skin. The antigen persists on monocytes cultured for greater than 4 wk, but it is not found on giant cells. The 3C10-1D9 determinant is carried by a 55 kD polypeptide, is expressed at approximately 40,000 copies per monocyte, and is protease sensitive. The antigen is clearly different from HLA-class II or Ia-like antigens that have been studied with a new monoclonal 9.3F10. The 9.3F10 antigen is found on B cells, dendritic cells and monocytes; is protease resistant, and occurs on a 33-29 kD doublet typical of class II products. The 3C10 monoclonal provides a clear distinction between human mononuclear phagocytes and dendritic cells. First, monocytes and lymphocytes can be eliminated from plastic-adherent mononuclear cells using 3C10, complement, and two previously described cytotoxic antibodies, BA-1 (anti-B cell) and Leu-1 (anti-T cell). As a result, the trace dendritic cell component of blood can be enriched to considerable purity (65-75%) and yield. Second, immunocytochemical staining of tissue sections reveals that 3C10+ macrophages are anatomically segregated from dendritic cells. Large numbers of 3C10+ cells are found in red pulp of spleen and in regions surrounding lymphatic channels of lymph node. However, 3C10+ macrophages are scarce in white pulp of spleen and the lymphocyte-rich cortex of node that are the sites where dendritic cells are localized. 3C10+ cells in skin are found in the dermis, particularly in leprosy infiltrates, but the Langerhans' cells of epidermis are 3C10-. The distinctive localization of macrophages and dendritic cells is consistent with their respective functions as effector and accessory cells in the immune response.


Pain ◽  
2018 ◽  
Vol 159 (7) ◽  
pp. 1325-1345 ◽  
Author(s):  
Pradipta Ray ◽  
Andrew Torck ◽  
Lilyana Quigley ◽  
Andi Wangzhou ◽  
Matthew Neiman ◽  
...  

2021 ◽  
Author(s):  
Stephanie M Zimmerman ◽  
Robin Fropf ◽  
Bridget R Kulasekara ◽  
Maddy Griswold ◽  
Oliver Appelbe ◽  
...  

Emerging spatial profiling technology has enabled high-plex molecular profiling in biological tissues, preserving the spatial and morphological context of gene or protein expression. Here we describe expanded chemistry for the Digital Spatial Profiling platform to quantify whole transcriptomes in human and mouse tissues using a wide range of spatial profiling strategies and sample types. We designed multiplexed in situ hybridization probe pools targeting the protein-coding genes in the human and mouse transcriptomes, hereafter referred to as the human or mouse Whole Transcriptome Atlas (WTA). We validated the human and mouse WTA assays using cell lines to demonstrate concordance with orthogonal gene expression profiling methods in profiled region sizes ranging from ~10-500 cells. By benchmarking against bulk RNAseq and single-molecule fluorescence in situ hybridization, we demonstrate robust transcript detection possible down to ~100 transcripts per region. To assess the performance of WTA across tissue and sample types, we applied WTA to biological questions in cancer, molecular pathology, and developmental biology. We show that spatial profiling with WTA can detect expected spatial gene expression differences between tumor and tumor microenvironment, identify spatial disease-specific heterogeneity in gene expression in histological structures of the human kidney, and comprehensively map transcriptional programs in anatomical substructures of nine organs in the developing mouse embryo. Digital Spatial Profiling technology with the WTA assays provides a flexible method for spatial whole transcriptome profiling applicable to diverse tissue types and biological contexts.


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