scholarly journals PAHs Target Hematopoietic Linages in Bone Marrow through Cyp1b1 Primarily in Mesenchymal Stromal Cells but Not AhR: A ReconstitutedIn VitroModel

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Catherine M. Rondelli ◽  
Michele Campaigne Larsen ◽  
Alhaji N’jai ◽  
Charles J. Czuprynski ◽  
Colin R. Jefcoate
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mouse Bone Marrow ◽  
Mesenchymal Progenitor Cells ◽  
Hematopoietic Progenitors ◽  
Developmental Factors ◽  
Enhanced Sensitivity ◽  
Colony Forming Units

7,12-Dimethylbenz(a)anthracene (DMBA) rapidly suppresses hematopoietic progenitors, measured as colony forming units (CFU), in mouse bone marrow (BM) leading to mature cell losses as replenishment fails. These losses are mediated by Cyp1b1, independent of the AhR, despite induction of Cyp1b1. BM mesenchymal progenitor cells (MPC) may mediate these responses since basal Cyp1b1 is minimally induced. PreB colony forming unit activity (PreB CFU) is lost within 24 hours in isolated BM cells (BMC) unless cocultured with cells derived from primary MPC (BMS2 line). The mouse embryonic OP9 line, which provides more efficient coculture support, shares similar induction-resistant Cyp1b1 characteristics. This OP9 support is suppressed by DMBA, which is then prevented by Cyp1b1 inhibitors. OP9-enriched medium partially sustains CFU activities but loses DMBA-mediated suppression, consistent with mediation by OP9 Cyp1b1. PreB CFU activity in BMC from Cyp1b1-ko mice has enhanced sensitivity to DMBA. BMC gene expression profiles identified cytokines and developmental factors that are substantially changed in Cyp1b1-ko mice. DMBA had few effects in WT mice but systematically modified many clustered responses in Cyp1b1-ko mice. Typical BMC AhR-responsive genes were insensitive to Cyp1b1 deletion. TCDD replicated Cyp1b1 interventions, suggesting alternative AhR mediation. Cyp1b1 also diminishes oxidative stress, a key cause of stem cell instability.

scholarly journals Multiple Myeloma Cells Alter Adipogenesis, Increase Senescence-Related and Inflammatory Gene Transcript Expression, and Alter Metabolism in Preadipocytes

2021 ◽  
Vol 10 ◽  
Author(s):  
Heather Fairfield ◽  
Samantha Costa ◽  
Carolyne Falank ◽  
Mariah Farrell ◽  
Connor S. Murphy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Lipid Accumulation ◽  
Expression Profiles ◽  
Adipogenic Differentiation ◽  
Gene Expression Profiles ◽  
Mouse Bone Marrow ◽  
Gene Transcript ◽  
Bone Marrow Mscs

Within the bone marrow microenvironment, mesenchymal stromal cells (MSCs) are an essential precursor to bone marrow adipocytes and osteoblasts. The balance between this progenitor pool and mature cells (adipocytes and osteoblasts) is often skewed by disease and aging. In multiple myeloma (MM), a cancer of the plasma cell that predominantly grows within the bone marrow, as well as other cancers, MSCs, preadipocytes, and adipocytes have been shown to directly support tumor cell survival and proliferation. Increasing evidence supports the idea that MM-associated MSCs are distinct from healthy MSCs, and their gene expression profiles may be predictive of myeloma patient outcomes. Here we directly investigate how MM cells affect the differentiation capacity and gene expression profiles of preadipocytes and bone marrow MSCs. Our studies reveal that MM.1S cells cause a marked decrease in lipid accumulation in differentiating 3T3-L1 cells. Also, MM.1S cells or MM.1S-conditioned media altered gene expression profiles of both 3T3-L1 and mouse bone marrow MSCs. 3T3-L1 cells exposed to MM.1S cells before adipogenic differentiation displayed gene expression changes leading to significantly altered pathways involved in steroid biosynthesis, the cell cycle, and metabolism (oxidative phosphorylation and glycolysis) after adipogenesis. MM.1S cells induced a marked increase in 3T3-L1 expression of MM-supportive genes including Il-6 and Cxcl12 (SDF1), which was confirmed in mouse MSCs by qRT-PCR, suggesting a forward-feedback mechanism. In vitro experiments revealed that indirect MM exposure prior to differentiation drives a senescent-like phenotype in differentiating MSCs, and this trend was confirmed in MM-associated MSCs compared to MSCs from normal donors. In direct co-culture, human mesenchymal stem cells (hMSCs) exposed to MM.1S, RPMI-8226, and OPM-2 prior to and during differentiation, exhibited different levels of lipid accumulation as well as secreted cytokines. Combined, our results suggest that MM cells can inhibit adipogenic differentiation while stimulating expression of the senescence associated secretory phenotype (SASP) and other pro-myeloma molecules. This study provides insight into a novel way in which MM cells manipulate their microenvironment by altering the expression of supportive cytokines and skewing the cellular diversity of the marrow.

scholarly journals Predicting the Remaining Lifespan and Cultivation-Related Loss of Osteogenic Capacity of Bone Marrow Multipotential Stromal Cells Applicable across a Broad Donor Age Range

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Sarah M. Churchman ◽  
Sally A. Boxall ◽  
Dennis McGonagle ◽  
Elena A. Jones
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Expression Profiles ◽  
Cpg Islands ◽  
Gene Expression Profiles ◽  
Donor Age ◽  
Diverse Range ◽  
Healthy Donors ◽  
Population Doublings ◽  
Age Range

Background and Objectives. Culture expanded multipotential stromal cells (MSCs) have considerable potential for bone regeneration therapy but their wider use is constrained by the lack of simple and predictive assays of functional potency. Extended passaging leads to loss of multipotency but speed of decline depends on MSC donor age. The aim of this study was to develop an assay predictive of MSC culture longevity applicable to a broad donor age range. Materials and Methods. Bone marrow (BM, n=7) was obtained from a diverse range (2–72 years) of healthy donors. MSCs were culture expanded to senescence and their osteoprogenitor content, gene expression profiles, epigenetic signature, and telomere behaviour were measured throughout. Output data was combined for modelling purposes. Results. Regardless of donor age, cultures’ osteoprogenitor content correlated better with remaining lifespan (population doublings before senescence, PD-BS) than proliferative history (accrued PDs). Individual gene’s expression or telomere length did not predict PD-BS but methylation of individual CpG islands did, PRAMEF2 in particular (r=0.775). Coupling the steep relationship of relative SPARC expression with PD-BS (r=-0.753) the formula SPARC × 1/PREMEF2 gave an improved correlation (r=-0.893). Conclusion. A formula based on SPARC mRNA and PRAMEF2 methylation may be used to predict remaining BM-MSC longevity and related loss of multipotentiality independent of donor age.

scholarly journals Age-Related Modulation of the Effects of Obesity on Gene Expression Profiles of Mouse Bone Marrow and Epididymal Adipocytes

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72367 ◽  
Author(s):  
Li-Fen Liu ◽  
Wen-Jun Shen ◽  
Masami Ueno ◽  
Shailja Patel ◽  
Salman Azhar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mouse Bone Marrow ◽  
Age Related

scholarly journals The Effects ofParacoccidioides brasiliensisInfection on GM-CSF- and M-CSF-Induced Mouse Bone Marrow-Derived Macrophage from Resistant and Susceptible Mice Strains

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Calliandra de Souza Silva ◽  
Aldo Henrique Tavares ◽  
Marcio Sousa Jeronimo ◽  
Yasmin Soares de Lima ◽  
Lorena da Silveira Derengowski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Expression Profiles ◽  
Paracoccidioides Brasiliensis ◽  
Gene Expression Profiles ◽  
Mouse Strains ◽  
Mouse Bone Marrow ◽  
Strongly Correlated ◽  
Gm Csf ◽  
Susceptibility And Resistance ◽  
Innate Tendency

Considering the importance of macrophages as the first line of defense against fungal infection and the different roles played by the two M1- and M2-like polarized macrophages, we decided to evaluate the effects ofParacoccidioides brasiliensisinfection on GM-CSF- and M-CSF-induced bone marrow-derived macrophages (BMM) from the A/J and B10.A mouse strains, an established model of resistance/susceptibility to PCM, respectively. Upon differentiation, the generated GM- or M-BMMs were characterized by morphological analyses, gene expression profiles, and cytokines production. Our main results demonstrate that GM-BMMs derived from A/J and B.10 produced high levels of pro- and anti-inflammatory cytokines that may contribute to generate an unbalanced early immune response. In accordance with the literature, the B10.A susceptible mice lineage has an innate tendency to polarize into M1-like phenotype, whereas the opposite phenotype occurs in A/J resistance mice. In this context, our data support that susceptibility and resistance are strongly correlated with M1 and M2 polarization, respectively.

Isolation of Multipotent Stromal Cells from Mouse Bone Marrow

BIO-PROTOCOL ◽  
2014 ◽  
Vol 4 (4) ◽  
Author(s):  
Aurélie Tormo ◽  
Moutih Rafei ◽  
Jean-François Gauchat
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Mouse Bone Marrow ◽  
Multipotent Stromal Cells
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