ATAC-seq of the granulopoiesis lineage from different organs
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE318435 | GEO | 2026/04/17
REPOSITORIES: GEO
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Project description:Normal human neutrophil development is a complex biological process, where the balance between cell proliferation, differentiation and apoptosis is tightly regulated by a transcriptional program that results in the production of appropriate numbers of circulating mature neutrophils. MicroRNAs (miRNAs) are small non-coding RNAs of 18~25 nt that affect cellular protein levels. Only limited data is available on miRNA expression patterns during normal granulocytic differentiation of primary human cells. We have examined miRNA expression patterns in distinct stages of granulocytic differentiation sorted from human bone marrow and identified highly stage-specific expressed miRNAs. Some of these differentially expressed miRNA are related to each other in terms of seed sequence (miRNA families) and location on the genome (miRNA clusters). These data reveal distinct expression patterns of specific miRNA sets that closely follow the transition of discrete maturation stages along the myeloblast-neutrophil pathway. In total 13 samples were measured, 2 myeloblast, 3 myeloblast/promyelocyte, 4 metamyelocytes and 3 neutrophils
2010-04-22 | E-GEOD-21437 | biostudies-arrayexpress
Project description:The current model of hematopoiesis only resolves the thymus around the production and establishment of the peripheral T cell pool. However, the role and in situ development of other immune subsets has been overlooked. We aim to demonstrate that during TL1A and IL-18 induced inflammation, the thymus is capable of producing other cell types such as neutrophils, monocytes, and macrophages and that these potentially have other functions aside from supporting T cell development as scavengers. Here we have proven that ex vivo and in vivo treatment with TL1A and IL-18 results in acute thymic atrophy by a massive loss of DP T cells and shrinking of the thymic lobe. By electron microscopy, flow cytometry and single cell we demonstrate that neutrophils are able to maturate inside the thymus lobe in a NOTCH-independent manner. We used fate-mapping tools to elucidate the origin of thymic neutrophils since we observed a great expansion in our culture that is isolated from the influx of BM progenitors. The Rag1-Cre Rosa26-YFP fate mapping model revealed that neutrophils share a common progenitor with T cells, while monocytes/macrophages do not. Furthermore, we found that most of the thymic GMPs (defined as Lin-Sca-1-c-Kit+CD16/32+CD34+) show history of Rag1 expression in comparison with bone marrow GMPs. Additionally, by using Ms4a3-Cre Rosa26Tdtomato fate mapping model we observed that there was not difference in Tdt labeling between the thymus and bone marrow, suggesting that thymic neutrophils still undergo conventional neutrophils pathway arising from GMPs. Moreover, we show that thymic-derived neutrophils are functional and are capable of forming extracellular neutrophils traps (NETs) similarly to benchmark peritoneal neutrophils. We found that the expansion of thymic neutrophils is GM-CSF dependent by using Csf2rb KO mice. Additionally, we identified DR3+ and IL-18Rα+ expressing subsets of ILCs and gdT cells as the cellular source GM-CSF. Lastly, in vivo treatment with TL1A+IL-18 lead to emergency granulopoiesis and an increase of neutrophils in all the organs investigated, including the thymus.
2024-09-05 | GSE244172 | GEO
Project description:Normal human neutrophil development is a complex biological process, where the balance between cell proliferation, differentiation and apoptosis is tightly regulated by a transcriptional program that results in the production of appropriate numbers of circulating mature neutrophils. MicroRNAs (miRNAs) are small non-coding RNAs of 18~25 nt that affect cellular protein levels. Only limited data is available on miRNA expression patterns during normal granulocytic differentiation of primary human cells. We have examined miRNA expression patterns in distinct stages of granulocytic differentiation sorted from human bone marrow and identified highly stage-specific expressed miRNAs. Some of these differentially expressed miRNA are related to each other in terms of seed sequence (miRNA families) and location on the genome (miRNA clusters). These data reveal distinct expression patterns of specific miRNA sets that closely follow the transition of discrete maturation stages along the myeloblast-neutrophil pathway.
2010-04-22 | GSE21437 | GEO
Project description:Emergency granulopoiesis refers to the increased production of neutrophils in bone marrow and their release into circulation induced by severe infection. Several studies point to a critical role for granulocyte colony-stimulating factor (G-CSF) as the main mediator of emergency granulopoiesis. However, the consequences of G-CSF stimulation on the transcriptome of neutrophils and their precursors have not yet been investigated in humans. Here, we examine the changes in mRNA expression induced by administration of G-CSF in vivo, as a model of emergency granulopoiesis in humans. Blood samples were collected from healthy individuals after five days of G-CSF administration. Neutrophil precursors were sorted into discrete stages of maturation by flow cytometry, and RNA was subjected to microarray analysis. mRNA levels were compared to previously published expression levels in corresponding populations of neutrophil precursors isolated from bone marrow of untreated, healthy individuals. 1110 mRNAs were differentially expressed more than 2-fold throughout terminal granulopoiesis. Major changes were seen in pathways involved in apoptosis, cytokine signaling, and Toll-like receptor pathways. In addition, G-CSF treatment reduced the levels of four out of five measured granule proteins in mature neutrophils including the proantibacterial protein hCAP-18, which was completely deficient in neutrophils from G-CSF-treated donors. These results indicate that multiple biological processes are altered in order to satisfy the increased demand for neutrophils during G-CSF-induced emergency granulopoiesis in humans.
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Project description:Sepsis, the dysregulated host response to infection leading to organ dysfunction, arises from diverse mechanisms that are poorly resolved by sepsis as a syndromic classification, confounding immunotherapy trials. Here we delineate neutrophil and granulopoietic disturbances underlying sepsis pathophysiology. We present a whole blood single-cell multiomic sepsis response atlas (272,993 cells, n=39 individuals), revealing multiple immature neutrophil populations that were collectively immunosuppressive, inhibiting CD4+ T cell proliferation and activation in co-culture. We traced this to altered granulopoiesis using single-cell multiomic mapping of circulating hematopoietic stem cells (HSCs) (29,366 cells, n=27). We show how these features are enriched in a subset of patients, resolving a specific poor outcome endotype (sepsis response signature SRS1). SRS1 patients have increased IL1R2+ immature neutrophils, epigenetic signatures of emergency granulopoiesis transcription factors in HSCs, and STAT3 features across infectious disease settings. Our findings delineate an immunohematopoietic axis, therapeutic targets and stratified medicine approach to sepsis.
2024-10-16 | GSE216009 | GEO
Project description:Sepsis, the dysregulated host response to infection leading to organ dysfunction, arises from diverse mechanisms that are poorly resolved by sepsis as a syndromic classification, confounding immunotherapy trials. Here we delineate neutrophil and granulopoietic disturbances underlying sepsis pathophysiology. We present a whole blood single-cell multiomic sepsis response atlas (272,993 cells, n=39 individuals), revealing multiple immature neutrophil populations that were collectively immunosuppressive, inhibiting CD4+ T cell proliferation and activation in co-culture. We traced this to altered granulopoiesis using single-cell multiomic mapping of circulating hematopoietic stem cells (HSCs) (29,366 cells, n=27). We show how these features are enriched in a subset of patients, resolving a specific poor outcome endotype (sepsis response signature SRS1). SRS1 patients have increased IL1R2+ immature neutrophils, epigenetic signatures of emergency granulopoiesis transcription factors in HSCs, and STAT3 features across infectious disease settings. Our findings delineate an immunohematopoietic axis, therapeutic targets and stratified medicine approach to sepsis.
2024-10-16 | GSE216007 | GEO
Project description:HSC (Sca+ SP) were isolated from 8-12 week C57B6 mice at various time points after treatment with 5-Fluorouracil. RNA was isolated from 50,000-100,000 FACS sorted cells and subjected to two rounds of T7 based linear amplification using Ambion's Message Amp kit. Two replicates from each time point were analyzed. http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371%2Fjournal.pbio.0020301 Keywords = HSC Keywords = proliferation Keywords = quiescence Keywords = 5-FU Keywords: time-course
2004-09-28 | GSE1559 | GEO
Project description:HSC (Sca+ SP) were isolated from 8-12 week C57B6 mice at various time points after treatment with 5-Fluorouracil. RNA was isolated from 50,000-100,000 FACS sorted cells and subjected to two rounds of T7 based linear amplification using Ambion's Message Amp kit. Two replicates from each time point were analyzed. http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371%2Fjournal.pbio.0020301
2007-11-15 | E-GEOD-1559 | biostudies-arrayexpress
Project description:We employed GeneChip analysis to investigate the global gene expression profiles of neutrophils from BM Gr-1high/CD48– neutrophils were sorted from the BM of C57BL/6 mice by FACS in two independent experiments
2014-01-06 | E-GEOD-53826 | biostudies-arrayexpress
Project description:Human telomerase reverse transcriptase (hTERT)-Immortalized cell line (T-HF) with or without DOX-induced KD of SSPR1 and SPT6 were infected with wild-type simplex virus 1 (HSV-1) strain F or with ICP22-null mutant at a multiplicity of infection (MOI) of 10. Omni-ATAC-seq libraries were prepared starting with 50,000 cells per condition following the protocol described by Corces, M., Trevino, A., Hamilton, E. et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat Methods 14, 959–962 (2017). https://doi.org/10.1038/nmeth.4396
2023-06-20 | GSE185236 | GEO