Interaction of bone marrow stroma and monocytes: bone marrow stromal cell lines cultured with monocytes
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE10595 | GEO | 2008/02/22
SECONDARY ACCESSION(S): PRJNA107753
REPOSITORIES: GEO
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Project description:The hematopoietic microenvironment consists of non-hematopoietic derived stromal elements and hematopoietic derived monocytes and macrophages which interact and function together to control the proliferation and differentiation of early blood-forming cells. Two human stromal cell lines (HS-5 and HS-27a) representing distinct functional components of this microenvironment have been extensively characterized and shown to influence monocyte gene expression. This series of gene expression profiles is intended to extend the previous studies and identify which gene expression changes may require cell-cell contact or occur in the stromal cells as a result of monocyte influence;or in the monocytes as a result of stormal influences. Experiment Overall Design: Two human bone marrow stromal cell lines (HS5 and HS27a) were cultured with and without monocytes (CD14+ cells) from 2 different donors. Experiment Overall Design: culture condition: stroma no monocytes: HS5-1, HS5-2, HS27a-1, HS27a-2 Experiment Overall Design: culture condition: stroma with monocytes: HS5-MO-1, HS5-MO-2, HS27a-MO-1, HS27a-MO-2 Experiment Overall Design: donor: donor 3: HS5-MO-1, HS27a-MO-1 Experiment Overall Design: donor: donor 4: HS5-MO-2, HS27a-MO-2 Experiment Overall Design: cell line: HS5: HS5-1, HS5-2, HS5-MO-1, HS5-MO-2 Experiment Overall Design: cell line: HS27a: HS27a-1, HS27a-2, HS27a-MO-1, HS27a-MO-2
2008-04-07 | E-GEOD-10595 | biostudies-arrayexpress
Project description:The bone marrow microenvironment is a complex mixture of cells that function in concert to regulate hematopoiesis. Cellular components include fixed nonhematopoietic stromal elements as well as monocytes and resident macrophages, which are derived from the hematopoietic stem cells. Although these monocyte-lineage cells are reported to modify stromal cell function, the reverse also occurs. Given the secretory capability of the monocyte/macrophage and their various potential functions, it is not surprising that stromal cells contained within a particular niche can modify monocyte gene expression and functional maturation. Keywords: cellular response to cell contact and secreted factors
2008-03-01 | GSE9390 | GEO
Project description:Two human stromal cell lines, HS-5 and HS-27a, represent functionally distinct components of the bone marrow microenvironment. A third influential component of the microenvironment is resident monocytes and macrophages. The baseline expression profile of normal peripheral blood monocytes was determined and their effect on the gene expression of the stromal cells was investigated in a co-culture sytem. Control RNA for all samples was Stratagene Universal human reference RNA. Keywords: Cell Line Comparison and Culture Comparison
2005-10-25 | GSE3472 | GEO
Project description:The bone marrow microenvironment is a complex mixture of cells that function in concert to regulate hematopoiesis. Cellular components include fixed nonhematopoietic stromal elements as well as monocytes and resident macrophages, which are derived from the hematopoietic stem cells. Although these monocyte-lineage cells are reported to modify stromal cell function, the reverse also occurs. Given the secretory capability of the monocyte/macrophage and their various potential functions, it is not surprising that stromal cells contained within a particular niche can modify monocyte gene expression and functional maturation. Experiment Overall Design: Monocytes were isolated from peripheral blood mononuclear cells from 2 different normal donors and cultured for 48h in conditioned medium (CM). The CM was collected from each of two functionally distinct human bone marrow stromal cell lines (HS5 and HS27a) representing different compartments of the bone marrow microenvironment (Roecklein BA, Torok-Storb B. Blood. 1995;85:997-1005). Four samples were analyzed, with two biological replicates for each CM.
2008-04-06 | E-GEOD-9390 | biostudies-arrayexpress
Project description:Retinoic acid signaling regulates monocyte differentiation into dendritic cells or macrophages. We used microarrays to uncover gene expression changes associated with retinoic acid exposure in mouse monocytes. The immunosuppressive tumor microenvironment (TME) is a major barrier to immunotherapy. Within solid tumors, why monocytes preferentially differentiate into immunosuppressive tumor associated macrophages (TAMs) but not immunostimulatory dendritic cells (DCs) remains unclear. Using multiple murine sarcoma models, we found that the TME induced retinoic acid (RA) production by tumor cells, which polarized intratumoral monocyte differentiation towards TAMs and away from DCs via suppression of DC-promoting transcription factor Irf4. Genetic inhibition of RA production by tumor cells or pharmacologic inhibition of RA signaling within TME increased stimulatory monocyte-derived cells, enhanced T cell-dependent anti-tumor immunity and demonstrated striking synergy with immune checkpoint blockade. Further, RA responsive gene signature in human monocytes correlated with an immunosuppressive TME in multiple human tumors. RA has been long considered as an anti-cancer agent, but our work demonstrates its tumorigenic capability via myeloid-mediated immune suppression and provides proof of concept for targeting this pathway for tumor immunotherapy.
2020-05-01 | GSE144609 | GEO
Project description:Ly6Clo monocytes are a myeloid subset that specializes in the surveillance of vascular endothelium. Ly6Clo monocytes have been shown to derive from Ly6Chi monocytes. Notch2 signaling has been implicated as a trigger for Ly6Clo monocyte development, but the basis for this effect is unclear. Here, we examined the impact of Notch2 signaling of myeloid progenitors on the development of Ly6Clo monocytes in vitro. Notch2 signaling induced by delta-like ligand 1 (DLL1) efficiently induced the transition of Ly6Chi TremL4– monocytes into Ly6Clo TremL4+ monocytes. We further discovered two additional transcriptional requirements for development of Ly6Clo monocytes. Deletion of Bcl6 from myeloid progenitors abrogated development of Ly6Clo monocyte development. IRF2 was also required for Ly6Clo monocyte development in a cell-intrinsic manner. DLL1-induced in vitro transition into Ly6Clo TremL4+ monocytes required IRF2 but unexpectedly could occur in the absence of Nur77 or Bcl6. These results imply a transcriptional hierarchy for these factors in controlling Ly6Clo monocyte development. This experiment compare RNA expression profiles between nonclassical monocytes and various cell types involved in their development.
2023-07-28 | GSE218503 | GEO
Project description:In mice, two restricted DC progenitors, macrophage-dendritic progenitor (MDP) and common dendritic cell progenitor (CDP) demonstrate increasing commitment of DC lineage as they sequentially lose granulocyte and monocyte potential respectively. Identifying these progenitors has enabled understanding of the role of DCs and monocytes in immunity and tolerance in mice. In humans, however, restricted monocyte and DC progenitors remain unknown. Progress in studying human DC development has been hampered by lack of an in vitro culture system that recapitulates in vivo DC hematopoiesis. Here we report a culture system that supports development of CD34+ hematopoietic stem cell progenitors into the three major human DC subsets, monocytes, granulocytes, NK and B cells. Using this culture system we defined the pathway for human DC development, and revealed the sequential origin of human DCs from increasingly restricted progenitors: a granulocyte-monocyte-DC progenitor (hGMDP) that develops into a monocyte-DC progenitor (hMDP) that develops into monocytes and a common DC progenitor (hCDP) that is restricted to produce the three major DC subsets. The phenotype of the DC progenitors partially overlaps with granulocyte monocyte progenitors (GMPs). These progenitors reside in human cord blood and bone marrow but not in the blood or lymphoid tissues in the steady state. We performed whole transcriptome expression analysis on monocytes and subsets of dendritic cells i.e. CD1c+ DCs, CD141+ DCs and CD303+ pDCs isolated from blood or differentiated in culture from cord blood CD34+ cells in presence of MS5 stromal cells and Flt3l, GM-CSF and SCF cytokines.
2015-01-22 | E-GEOD-65128 | biostudies-arrayexpress
Project description:Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar, but distinct, monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of “neutrophil-like” monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection.
2017-11-13 | GSE104478 | GEO
Project description:Diminishing potential to replace damaged tissues is a hallmark for aging of somatic stem cells, but the mechanisms leading to aging remain elusive. We performed a proteome-wide analysis of human hematopoietic stem and progenitor cells (CD34+) along with five other cell types that constitute the bone marrow niche, namely, lymphocytes and precursors; monocytes/macrophages and precursors; granulocytic precursors and erythroid precursors, as well as mesenchymal stem/stromal cells. In total, we analyzed 270 samples from 59 human subjects. The data represents a valuable resource for further in-depth mechanistic analyses, and for validation of knowledge gained from animal models.
2018-07-20 | PXD007048 | Pride
Project description:Monocytes are circulating myeloid immune precursor cells that are generated in the bone marrow (BM). Upon their release into the circulation, monocytes are recruited to inflammatory sites, where they differentiate into monocyte-derived effector cells. In absence of overt inflammation, monocytes also extravasate into selected tissues, where they complement tissue-resident macrophage compartments. Recent studies have uncovered binary developmental trajectories of monocytes in the BM with Neutrophil-like (NeuMo) and dendritic cell (DC)-like (DCMo) monocytes differentiating downstream of granulocyte-macrophage progenitors (GMP) and macrophage-dendritic cell progenitors (MDP), respectively (Weinreb et al., 2020; Yanez et al., 2017). Yet, the molecular cues that dictate BM monocyte differentiation remain incompletely understood. The COMMD (copper metabolism MURR1 domain) family includes 10 evolutionarily conserved proteins. Functions of COMMD proteins are still being defined, but they seem to play non-redundant roles in regulating transcription and protein trafficking. Utilizing conditional COMMD10 knockout mice we uncovered a role for COMMD10 in limiting inflammasome activation in Ly6Chi monocytes during experimental sepsis and colitis (Mouhadeb et al., 2018), and in supporting phagolysosomal biogenesis and maturation in KCs and BM-derived macrophages infected with Staphylococcus aureus (Ben Shlomo et al., 2019). Hence, these studies mark COMMD10 as a candidate mediator of monocyte and macrophage fate and immune responses. Here we studied the effect of COMMD10-deficiency on Ly6Chi monocyte differentiation. We show that COMMD10-deficiency in steady state Ly6Chi monocytes promotes a differentiation bias towards NeuMo fate.
2021-10-05 | GSE183495 | GEO