Distinct Gene Expression Pattern of Malignant Hematopoietic Stem and Progenitor Cells in Polycythemia Vera

Abstract TCR zeta chain of TCR-CD3 receptor complex is though to be critical for T cells development and T cell effector function. The absence of TCR zeta chain not only influences the TCR expression on the cell membrane, but also impairs the proliferative response and the level of activation of mature T cells. Recently, the abnormal expression of TCR zeta chain was found different disease, for example in hematological malignancy. In the present study, we analyzed the expression level of TCR zeta chain gene in T cells from patients with aplastic anemia (AA) and polycythemia vera (PV), thereby to estimate the feature of T cells activation status. Real-time PCR with SYBR Green I technique was used for detecting the expression level of TCR zeta chain gene in peripheral blood mononuclear cells of patients with AA (25 cases),PV (12 cases), and 30 normal individuals. β2-microglobulin gene was used as an endogeneous reference. Evaluation of TCR zeta chain gene expression level were used the 2−ΔΔCt method. Compared with the normal control, TCR zeta chain gene expression level could be divided into two groups: 10 patients with AA (40%) and 5 patients with PV (41.7%) were over expression, while 15 patients with AA (60%) and 7 patients with PV (58.3%) were down expression. The expression level of TCR zeta gene is nonsignificat age-associated in both AA and PV patients. Moreover, the expression level of TCR zeta gene is nonsignificant age-associated or gender-link in T cells from patients with AA. The signaling pathway of T cells activation might display some disorder in patients with AA or PV. The effect of the change of TCR zeta chain gene expression pattern in AA and PV patients should be further confirmed.

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Extracellular vesicles of stromal origin target and support hematopoietic stem and progenitor cells

The Journal of Cell Biology ◽

10.1083/jcb.201601109 ◽

2017 ◽

Vol 216 (7) ◽

pp. 2217-2230 ◽

Cited By ~ 19

Author(s):

Gregoire Stik ◽

Simon Crequit ◽

Laurence Petit ◽

Jennifer Durant ◽

Pierre Charbord ◽

...

Keyword(s):

Gene Expression ◽

Progenitor Cells ◽

Extracellular Vesicles ◽

Ex Vivo ◽

Fetal Liver ◽

Critical Role ◽

Molecular Signature ◽

Hematopoietic Stem ◽

Stem And Progenitor Cells

Extracellular vesicles (EVs) have been recently reported as crucial mediators in cell-to-cell communication in development and disease. In this study, we investigate whether mesenchymal stromal cells that constitute a supportive microenvironment for hematopoietic stem and progenitor cells (HSPCs) released EVs that could affect the gene expression and function of HSPCs. By taking advantage of two fetal liver–derived stromal lines with widely differing abilities to maintain HSPCs ex vivo, we demonstrate that stromal EVs play a critical role in the regulation of HSPCs. Both supportive and nonsupportive stromal lines secreted EVs, but only those delivered by the supportive line were taken up by HSPCs ex vivo and in vivo. These EVs harbored a specific molecular signature, modulated the gene expression in HSPCs after uptake, and maintained the survival and clonogenic potential of HSPCs, presumably by preventing apoptosis. In conclusion, our study reveals that EVs are an important component of the HSPC niche, which may have major applications in regenerative medicine.

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Differential Gene Expression Underlying the Functional Distinctions of Primary Human CD34+Hematopoietic Stem and Progenitor Cells from Peripheral Blood and Bone Marrow

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2003.tb03237.x ◽

2003 ◽

Vol 996 (1) ◽

pp. 89-100 ◽

Cited By ~ 15

Author(s):

ULRICH STEIDL ◽

RALF KRONENWETT ◽

RAINER HAAS

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Progenitor Cells ◽

Differential Gene Expression ◽

Peripheral Blood ◽

Hematopoietic Stem ◽

Human Cd34 ◽

Stem And Progenitor Cells ◽

Differential Gene

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Lincrna Hotset Regulates Hox Gene Transcription and Promotes Early Hematopoietic Fates

Blood ◽

10.1182/blood.v124.21.1573.1573 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1573-1573

Author(s):

Changwang Deng ◽

Ying Li ◽

Besabeh Tusi ◽

Wei Jian ◽

Bhavita Patel ◽

...

Keyword(s):

Gene Expression ◽

Embryonic Development ◽

Progenitor Cells ◽

Gene Transcription ◽

Three Dimensional ◽

Embryoid Bodies ◽

Hematopoietic Differentiation ◽

Hematopoietic Stem ◽

Hematopoietic Lineage ◽

Stem And Progenitor Cells

Abstract Mammalian genomes encode tens of thousands of long intergenic noncoding RNAs (lincRNAs). Accumulated evidence suggests that many of lincRNAs are expressed in a development- or tissue-specific manner. However, it remains largely unknown how lincRNAs reprogram lineage-specific gene expression and regulate lineage-specific differentiation processes during early embryonic development. It is also important to identify specific lincRNA(s) that is involved in early hematopoietic lineage formation and differentiation. Here, we reported a HoxB locus-associated lincRNA HOTSET that is conservatively expressed in both mouse and human hematopoietic stem and progenitor cells (HS/PCs). During embryonic development, HOTSET RNA is dramatically induced upon embryoid body (EB) hematopoietic differentiation. Expression of HOTSET RNA is required for development of the mesoderm-derived Flk1+ bipotential precursors of blood and endothelium lineages and CD41+/c-Kit+ hematopoietic stem and progenitor cells. We demonstrated that HOTSET RNA directly interacts with the SET domains of Setd1a and MLL1 histone methyltransferases in a sense-strand dependent manner. HOTSET RNA directly binds to the HoxB1-6 gene promoters and recruits the Setd1a/MLL1 complexes to the anterior HoxB locus upon differentiation. Furthermore, HOTSET RNA mediated H3K4 methylation is essential for long-range chromatin loops that bring anterior HoxB genes into a close proximity with HOTSET RNA locus and for subsequent activation of anterior HoxB gene expression. In addition, knockdown of HOTSET RNA disrupts the recruitment of the Setd1a/MLL1 complexes, H3K4me3 levels, the three-dimensional chromatin architecture, and HoxB gene transcription at the HoxB gene cluster. Depletion of HOTSET RNA also impairs differentiation of the CD41+/c-Kit+ HS/PC population and hematopoietic transcription factor and signaling networks required for early hematopoietic differentiation. Importantly, re-expression of HoxB2-4 genes in the HOTSET-depleted embryoid bodies rescues the expression of core hematopoietic transcription factors as well as the Flk1+ mesoderm-derived precursors and CD41+/c-Kit+ HS/PCs that undergo hematopoietic differentiation. Thus, HOTSET plays an important role in early hematopoietic lineage commitment by shaping the three-dimensional chromatin landscape in the HoxB locus to activate anterior HoxB genes that subsequently modulate lineage-specific transcription networks during hematopoietic development. Disclosures No relevant conflicts of interest to declare.

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