scholarly journals IgA Plasma Cells Are Long-Lived Residents of Gut and Bone Marrow That Express Isotype- and Tissue-Specific Gene Expression Patterns

2021 ◽  
Vol 12 ◽  
Author(s):  
Joel R. Wilmore ◽  
Brian T. Gaudette ◽  
Daniela Gómez Atria ◽  
Rebecca L. Rosenthal ◽  
Sarah Kim Reiser ◽  
...  

Antibody secreting plasma cells are made in response to a variety of pathogenic and commensal microbes. While all plasma cells express a core gene transcription program that allows them to secrete large quantities of immunoglobulin, unique transcriptional profiles are linked to plasma cells expressing different antibody isotypes. IgA expressing plasma cells are generally thought of as short-lived in mucosal tissues and they have been understudied in systemic sites like the bone marrow. We find that IgA+ plasma cells in both the small intestine lamina propria and the bone marrow are long-lived and transcriptionally related compared to IgG and IgM expressing bone marrow plasma cells. IgA+ plasma cells show signs of shared clonality between the gut and bone marrow, but they do not recirculate at a significant rate and are found within bone marrow plasma cells niches. These data suggest that systemic and mucosal IgA+ plasma cells are from a common source, but they do not migrate between tissues. However, comparison of the plasma cells from the small intestine lamina propria to the bone marrow demonstrate a tissue specific gene transcription program. Understanding how these tissue specific gene networks are regulated in plasma cells could lead to increased understanding of the induction of mucosal versus systemic antibody responses and improve vaccine design.

1997 ◽  
Vol 272 (7) ◽  
pp. 4287-4294 ◽  
Author(s):  
Shi-Fang Yan ◽  
Yu Shan Zou ◽  
Monica Mendelsohn ◽  
Yun Gao ◽  
Yoshifumi Naka ◽  
...  

2015 ◽  
Vol 7 (4) ◽  
pp. 1082-1097 ◽  
Author(s):  
Mihaela Pavlicev ◽  
Kaori Hiratsuka ◽  
Kayleigh A. Swaggart ◽  
Caitlin Dunn ◽  
Louis Muglia

1987 ◽  
Vol 93 (5) ◽  
pp. 1014-1020 ◽  
Author(s):  
Neal S. Leleiko ◽  
Beth A. Martin ◽  
Martin Walsh ◽  
Philip Kazlow ◽  
Simon Rabinowitz ◽  
...  

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 570
Author(s):  
Peter Briggs ◽  
A. Louise Hunter ◽  
Shen-hsi Yang ◽  
Andrew D. Sharrocks ◽  
Mudassar Iqbal

Many biological studies of transcriptional control mechanisms produce lists of genes and non-coding genomic intervals from corresponding gene expression and epigenomic assays. In higher organisms, such as eukaryotes, genes may be regulated by distal elements, with these elements lying 10s–100s of kilobases away from a gene transcription start site. To gain insight into these distal regulatory mechanisms, it is important to determine comparative enrichment of genes of interest in relation to genomic regions of interest, and to be able to do so at a range of distances. Existing bioinformatics tools can annotate genomic regions to nearest known genes, or look for transcription factor binding sites in relation to gene transcription start sites. Here, we present PEGS (Peak set Enrichment in Gene Sets). This tool efficiently provides an exploratory analysis by calculating enrichment of multiple gene sets, associated with multiple non-coding elements (peak sets), at multiple genomic distances, and within topologically associated domains. We apply PEGS to gene sets derived from gene expression studies, and genomic intervals from corresponding ChIP-seq and ATAC-seq experiments to derive biologically meaningful results. We also demonstrate an extended application to tissue-specific gene sets and publicly available GWAS data, to find enrichment of sleep trait associated SNPs in relation to tissue-specific gene expression profiles.


2017 ◽  
Author(s):  
Shuaishuai Teng ◽  
Yang Li ◽  
Ming Yang ◽  
Rui Qi ◽  
Yiming Huang ◽  
...  

SUMMARYTumor metastasis is the cause of death for 90% of cancer patients, and no currently-available therapies target this multi-step process in which cancer cells spread from the local tissue of a primary tumor to distant organs where they establish secondary tumors1. Although epithelial-to-mesenchymal transition2, tumor-secreted exosomes3, epigenetic regulators as well as other genes4-8 have been implicated in metastasis, little is known about how cells adapt to and colonize new tissue environments. Here, we show that the epigenetics-mediated reprogramming of tissue-specific gene transcription in cancer cells promotes metastasis. Using colorectal cancer (CRC) as a model, we found in both clinical and cell line studies that metastatic CRC cells lose their colon-specific gene transcription program and gain a liver-specific gene transcription program as they metastasize in the liver. Further, we found this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical and super-enhancers. Chemical inhibition of enhancer activity disrupts the ability of cells to execute altered transcription programs and consequently inhibits metastasis. Binding motif analysis of the enhancers in liver metastatic CRC cells identified the liver-specific transcription factor FOXA2 as a key regulator, and knocking down of FOXA2 expression prevents the colonization of metastatic CRC cells in the liver of a mice xenograft model. These results, together with additional observations of similar reprogramming in several cohorts of clinical CRC tumor samples and in multiple other forms of metastatic cancers, indicate that this reprogramming may be a common feature of metastasis in multiple cancers and suggest the targeted disruption of this epigenetic reprogramming as a strategy for the development of therapies to treat metastasis, the leading cause of cancer-related mortality.


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