scholarly journals Differential expression of lymphoid and myeloid markers on differentiating hematopoietic stem cells in normal and tumor-bearing adult human liver

Hepatology ◽  
2000 ◽  
Vol 31 (6) ◽  
pp. 1251-1256 ◽  
Author(s):  
Lucy Golden-Mason ◽  
Michael P. Curry ◽  
Niamh Nolan ◽  
Oscar Traynor ◽  
Gerry McEntee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Differential Expression ◽  
Human Liver ◽  
Hematopoietic Stem ◽  
Adult Human ◽  
Tumor Bearing

scholarly journals In vitro evidence for the presence of hematopoietic stem cells in the adult human liver

Hepatology ◽  
1999 ◽  
Vol 29 (4) ◽  
pp. 1193-1198 ◽  
Author(s):  
Orla M. Crosbie ◽  
Maura Reynolds ◽  
Gerry McEntee ◽  
Oscar Traynor ◽  
John E. Hegarty ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Human Liver ◽  
Hematopoietic Stem ◽  
Adult Human

The differentiation of hematopoietic stem cells was reprogrammed in advanced tumor-bearing mice

2020 ◽  
Author(s):  
Jicong Du ◽  
Penglin Xia ◽  
Yuan Gao ◽  
Ying Cheng ◽  
Ruling Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cancer Progression ◽  
Multilineage Differentiation ◽  
Mice Model ◽  
Hematopoietic Stem ◽  
Culture Techniques ◽  
Tumor Bearing ◽  
Advanced Tumor

Abstract Background: Hematopoiesis and the differentiation of HSC have been proved to not only play important roles in cancer progression but also be changed or reprogrammed by the tumor microenvironment itself. In this study, we investigated the changes of HSCs differentiation in advanced tumor-bearing mice. Methods: The tumor-bearing mice model was established by subcutaneously inoculating with xenografts of B16-F10 mouse melanoma cells into the right back of male wild-type C57BL/6 mice. Hematopoietic stem cells and multilineage differentiation were evaluated using blood routine, HE-staining, flow cytometry assay and HSCs culture techniques. Results: The multilineage differentiation of hematopoietic stem cells was reprogrammed in vivo . Especially, the differentiations of megakaryocyte and erythrocyte were blocked , while myeloid cell and lymphoid cell differentiation was encouraged in advanced tumor-bearing mice. Conclusion: In this study we showed the potential mechanism of hematopoietic disorder in tumor condition from a respective of hematopoietic stem cell and multilineage differentiation, which provided new knowledge regarding cachexia.

Characterization of Hematopoietic and Non-Hematopoietic Stem/Progenitor Cells in Freshly Isolated Adult Human Bone Marrow Using an 8-Color Flow Cytometric Assay.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4045-4045
Author(s):  
Ferda Tekinturhan ◽  
Ludovic Zimmerlin ◽  
Vera S. Donnenberg ◽  
Melanie E. Pfeifer ◽  
Darlene A. Monlish ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Progenitor Cell ◽  
P Value ◽  
Hematopoietic Stem ◽  
Adult Human

Abstract Bone marrow (BM) contains hematopoietic stem cells (HSCs), which can give rise to all mature blood cells and marrow stromal cells as well. Recently, it has been shown that non-hematopoietic stem/progenitor cells which can differentiate into non-hematopoietic tissues also reside in the BM. Although culture expanded cells have been studied in great detail, little is known about the phenotype and quantity of these cells in freshly harvested adult human BM. The aim of this study is to isolate and characterize hematopoietic and non-hematopoietic stem/progenitor cells in adult human BM by comparing two different isolation techniques and their effects on the yield of hematopoietic, mesenchymal and endothelial stem/progenitor cell populations. BM samples were collected mechanically from isolated rib specimens obtained during lung resection (n=10), or from BM aspirates harvested from the humerus of orthopedic patients (n=17). BM mononuclear cells were purified on a Ficoll/Hypaque density gradient and stained simultaneously using CD105 FITC, CD73 PE, CD34 ECD, CD90 PE.Cy5, CD117 PE.Cy7, CD133 APC, CD45 APC.Cy7 and DAPI as a marker of nucleated cells. 2–15 million cells per sample were acquired on a Dako CyAn cytometer and the data were analyzed offline using prototype analytical software (Venturi, Applied Cytometry Systems). The significant difference in the percentage of the CD45 − singlets (non-hematopoietic cells) between BM aspirates and rib-derived samples indicates hemodilution in the bone marrow aspirates. Although we have observed a slight difference in the mean of hematopoietic stem cell content between samples, it was not statistically significant. According to our results, the quantity of mesenchymal stem cells was higher in rib-derived BM than BM aspirates (p value=0.028). The expression of some stem/progenitor cell markers, such as CD90 (Thy-1), CD117 (c-Kit) and CD133 remained similar for all cell types. Our results are shown in the table below. Surface Antigens RibBM (n=10)¥ BMA (n=17)¥ p Value % % Total Cells CD45- of nucleated cells 15.3 ± 7.9 5.7 ± 5.2 0.004 CD34+ Hematopoietic Stem Cells (HSCs)* CD34 of CD45+ 1.7 ± 1.48 2.6 ± 2.0 0.883 CD117 74.6 ± 31.3 53.3 ± 18.8 0.073 CD90 60.3 ± 44.5 35.9 ± 36.5 0.134 CD133 70.3 ± 31.8 62.3 ± 21.4 0.443 Endothelial Progenitor Cells (EPCs)* EPCs of nucleated cells 0.05 ± 0.03 0.12 ± 0.2 0.323 CD117 81.3 ± 29.8 78.1 ± 20.2 0.746 CD90 66.7 ± 39.7 53.7 ± 31.4 0.356 CD133 45.9 ± 32.7 33.9 ± 22.0 0.265 Mesenchymal Stem Cells (MSCs)* MSCs of nucleated cells 0.086 ± 0.14 0.008 ± 0.01 0.028 CD117 60.2 ± 36.8 49.8 ± 34.3 0.471 CD90 66.0 ± 27.7 65.7 ± 29.1 0.981 CD133 37.8 ± 27.4 39.9 ± 28.9 0.857 RibBM: Rib-derived BM, BMA: Bone Marrow Aspirate ¥Data are given as mean ± SD. *CD90, CD117 and CD133 expressions are shown for each stem/progenitor fraction: Hematopoietic stem cells (CD34 + CD45 + and light scatter properties according to the ISHAGE protocol), endothelial progenitor cells (CD34bright CD45 − CD105 +) and mesenchymal stem cells (CD34 − CD45 − CD73 + CD105 +).

scholarly journals Differential Expression of Novel Potential Regulators in Hematopoietic Stem Cells

PLoS Genetics ◽  
2005 ◽  
Vol 1 (3) ◽  
pp. e28 ◽  
Author(s):  
E. Camilla Forsberg ◽  
Susan S Prohaska ◽  
Sol Katzman ◽  
Garrett C Heffner ◽  
Josh M Stuart ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Differential Expression ◽  
Hematopoietic Stem

scholarly journals A Unique Crosstalk between Tumor Cells and Hematopoietic Stem Cells Reveals a Myeloid Differentiation Pattern Signature Contributing to Metastasis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2465-2465
Author(s):  
Ksenia Magidey ◽  
Ksenya Kveler ◽  
Rachelly Normand ◽  
Tongwu Zhang ◽  
Michael Timaner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Tumor Cells ◽  
Expression Patterns ◽  
Cell Types ◽  
Myeloid Differentiation ◽  
Hematopoietic Stem ◽  
Tumor Bearing ◽  
Differentiation Pattern

Metastasis is the major cause of death in cancer patients. Recent studies have demonstrated that the crosstalk between different host and tumor cells in the tumor microenvironment regulates tumor progression and metastasis. Specifically, immune cell myeloid skewing is a prominent promoter of metastasis. While previous studies have demonstrated that the recruitment of myeloid cells to tumors is a critical step in dictating tumor fate, the reservoir of these cells in the bone marrow (BM) compartment and their differentiation pattern has not been explored. Here we utilized a unique model system consisting of tumor cell clones with low and high metastatic potential (met-low and met-high, respectively) derived from melanoma and breast carcinoma cell lines. Hematopoietic stem cells (HSCs) and their early progenitor subset were defined as Lin-/Sca1+/CD117+, representing LSK cells. BM transplantation experiments using GFP-positive LSK cells derived from met-low and met-high tumor bearing mice were carried out to study lineage differentiation. The genetic signatures of LSK cells were analyzed by single cell RNA-sequencing (scRNA-seq). This analysis included unbiased automated annotation of individual cell types by correlating single-cell gene expression with reference transcriptomic data sets (SingleR algorithm) in order to evaluate the proportions of cell types in BM and reveal cell type-specific differentially expressed genes. Expression patterns of proteins originated from tumor cells were analyzed using a range of multi-omics techniques including nanostring, protein array, and mass spectrometry analysis. Tumor proteomic data was integrated with differential receptor expression patterns in BM cell types to reveal novel crosstalk between tumor cells and HSCs in the BM compartment. Mice bearing met-high tumors exhibited a significant increase in the percentage of LSK cells in the BM in comparison to tumor-free mice or mice bearing met-low tumors. These results were confirmed by functional CFU assays of peripheral blood of met-high compared to met-low tumor bearing mice. In addition, mice that underwent BM transplantation with GFP-positive LSK cells obtained from met-high inoculated donors exhibited an increased percentage of circulating GFP-positive myeloid cells in comparison to counterpart mice transplanted with LSK cells from met-low inoculated donors. Moreover, scRNA-seq analysis of LSK cells obtained from the BM of met-low and met-high tumor bearing mice revealed that met-high tumors induce the enrichment of monocyte-dendritic progenitor population (MDP), confirmed also by flow cytometry. To uncover the possible factors involved in myeloid programming of LSK cells, we performed a proteomic screen of tumor conditioned medium and integrated the results with the scRNA-seq data analysis. This analysis revealed that the IL-6-IL-6R axis is highly active in LSK-derived MDP cells from mice bearing met-high tumors. An adoptive transfer experiment using MDP-GFP+ cells obtained from BM of met-high tumor bearing mice demonstrated that met-high tumors directly dictate HSC fate decision towards myeloid bias, resulting in increased metastasis. Evidently, blocking IL-6 in mice bearing met-high tumors reduced the number of MDP cells, and consequently decreased metastasis. Our study reveals a unique crosstalk between tumor cells and HSCs. It provides new insight into the mechanism by which tumors contribute to the presence of supporting stroma. Specifically, tumors secreting IL-6 dictate a specific genetic signature in HSCs that programs them towards myeloid differentiation, thereby inducing a metastatic switch. Disclosures No relevant conflicts of interest to declare.

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