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Gene expression of human littoral cells and splenic vascular endothelial cells from the spleens of normal individuals and patients with myelofibrosis

ABSTRACT: Gene expression of human littoral cells and splenic vascular endothelial cells from the spleens of normal individuals and patients with myelofibrosis

PROVIDER: PRJNA417120 | ENA |

REPOSITORIES: ENA

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Gene expression of human littoral cells and splenic vascular endothelial cells from the spleens of normal individuals and patients with myelofibrosis

Project description:The vascular lining cells in the human spleens include littoral cells (LCs) and other splenic vascular endothelial cells (SVECs). LCs that comprise about 30 percent of the splenic red pulp are specialzed endothelial cells distinct from SVECs. They line the splenic sinusoids and function as the filters and scavengers for senescent or altered red blood cells. Patients with advanced forms of myelofibrosis (MF) often develope extramedullary hematopoiesis in the spleen.Vascular lining cells within MF spleens are thought to serve as a supportive microenvironment for MF hematopoietic cells. In this study we isolated MF and normal LCs and SVECs from human spleens using immunostaining and flow cytometric sorting and used microarrays to analyze the underling mechanism of LCs' unique functions that distinguish them from SVECs, and the properties of MF LCs and SVECs and their contributions to the microenvironment of MF spleens.

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Gene expression of human splenic littoral cells compared with splenic vascular endothelial cells

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Spleens of myelofibrosis patients contain malignant hematopoietic stem cells.

Project description:Cancer stem cell behavior is thought to be largely determined by intrinsic properties and by regulatory signals provided by the microenvironment. Myelofibrosis (MF) is characterized by hematopoiesis occurring not only in the marrow but also in extramedullary sites such as the spleen. In order to study the effects of these different microenvironments on primitive malignant hematopoietic cells, we phenotypically and functionally characterized splenic and peripheral blood (PB) MF CD34+ cells from patients with MF. MF spleens contained greater numbers of malignant primitive HPCs than PB. Transplantation of PB MF CD34+ cells into immunodeficient (NOD/SCID/IL2Rγ(null)) mice resulted in a limited degree of donor cell chimerism and a differentiation program skewed toward myeloid lineages. By contrast, transplanted splenic MF CD34+ cells achieved a higher level of chimerism and generated both myeloid and lymphoid cells that contained molecular or cytogenetic abnormalities indicating their malignant nature. Only splenic MF CD34+ cells were able to sustain hematopoiesis for prolonged periods (9 months) and were able to engraft secondary recipients. These data document the existence of MF stem cells (MF-SCs) that reside in the spleens of MF patients and demonstrate that these MF-SCs retain a differentiation program identical to that of normal hematopoietic stem cells.

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Genomic characterization of spleens in patients with myelofibrosis.

Project description: Not available

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Gene expression data from WT and Klf3 KO mouse CD19+ splenic B cells

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Comparison of gene expression in megakaryocytes derived from primary myelofibrosis or healthy individuals

Project description:CD34+ cells from healthy individuals or those with primary myelofibrosis were cultured ex vivo under conditions to derive megakaryocytes. Following culture, megakaryocytes were purified by flow cytometry. The gene expression in these cells was determined by Illumina microarray analysis. Note that samples JC1-12 were run at a different time than JC13-24. Investigators may wish to perform the analysis of the two sets independently.

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