Murine mesenchymal and embryonic stem cells express a similar Hox gene profile

Phinney, Donald G.; Gray, Andrew; Hill, Katy; Pandey, Amitabh C.

doi:10.1016/j.bbrc.2005.10.140

Cited by 30 publications

(24 citation statements)

References 29 publications

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“…As recently published by Bruns et al, 24 microarray results showed the strong down-regulation of most TFs involved in self-renewal (namely GATA-2, 44 Bmi1, 45 LMO2, 46 HoxA5, 47 HoxB2, 48 HoxA9, 49 For 50 ) in CML versus normal CD34 ϩ cells ( Figure 5A). Consistently, transcripts for the HSC marker CD133 (PROM1), as well as L-selectin (SELL) and CD53 molecules, whose expression has been correlated to the maintenance of the stemness features, 24 were down-regulated in CML subpopulations ( Figure 5A).…”

Section: Self-renewal and Myeloid Commitment Capacitysupporting

confidence: 75%

“…Complete Molecular response: samples negative by RQ-PCR were analyzed by nested PCR and a complete molecular response was defined as nested PCR negativity. 48 Samples showing less than 1000 copies of ABL transcript were not considered evaluable and are not included in the analysis (range of ABL copies for CD34 ϩ cells was 2998-30 792; range for CD34 Ϫ cells was 3425-18 693). The number of cells analyzed was (range) 118 000-860 000 and 130 000-1 100 000 for CD34 ϩ and CD34 Ϫ , respectively.…”

Section: Discussionmentioning

confidence: 99%

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Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34− cell population with intrinsic resistance to imatinib

Lemoli

Salvestrini

Bianchi

et al. 2009

Blood

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IntroductionSeveral studies have demonstrated that normal hematopoietic stem cells (HSCs) exist in 2 functional states that can be distinguished based on CD34 expression. 1 CD34 Ϫ cells represent a kinetically and functionally resting stem cell subset that needs to be activated to generate a CD34 ϩ cell population with high proliferative and engraftment potential. 2,3 Acquisition of CD34 expression on human HSCs is associated with in vitro hematopoietic activity and cell-cycle recruitment. 4 CD34 Ϫ /CD34 ϩ transition results in metabolic activation and down-regulation of growth-inhibitory pathways, and CD34 ϩ stem cells show a significant up-regulation of self-renewal-, commitment-, and engraftment-related genes. 5 No data are presently available on the existence of a stem cell population devoid of CD34 expression in leukemic hematopoiesis.Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder of HSCs that have acquired a BCR-ABL fusion gene. The encoded 210-kDa protein has constitutively elevated tyrosine kinase activity that results in a large variety of biochemical changes in leukemic stem cells (LSCs) mainly inducing growth factor-independent proliferation, inhibition of apoptosis, and alteration of adhesive properties. 6 There is an increasing body of evidence indicating that, similar to normal hematopoiesis, a kinetically quiescent stem cell population can be isolated within the CD34 ϩ LSC compartment. 7 These G 0 CML cells are able to repopulate immunodeficient mice 8 and show a different transcriptional profile from dividing CD34 ϩ cells. 9 More importantly, the dissection of the stem cell pool in CML has allowed the characterization of subsets of CD34 ϩ LSCs resistant, in vitro and in vivo, to targeted therapies with BCR-ABL inhibitors. [10][11][12] Multiple mechanisms of drug resistance have been described, including kinetic quiescence per se, 10 increased expression level of BCR-ABL, and altered expression of ABCB1, ABCG2, and OCT1 cell membrane drug transporter genes in the most primitive CD34 ϩ /CD38 Ϫ LSCs. 13 Taken together, these findings stress the importance of gaining further understanding of the molecular and functional properties of the stem cell compartment in CML, in view of the development of more effective therapies.To this end, in the present study, we assessed the gene expression profile and the functional characteristics of a novel Lin Ϫ CD34 Ϫ stem cell population in CML patients at diagnosis. Our data demonstrate that approximately one-third of Lin Ϫ CD34 Ϫ cells are leukemic and capable of engraftment in immunodeficient mice. Overall, molecular analysis showed 1827 transcripts differentially expressed in CML HSC subpopulations compared with normal counterparts, genes affecting many cellular functions associated with the neoplastic phenotype. Microarray data also highlighted the highest transcriptome differences between CML Lin Ϫ CD34 Ϫ cells and their normal counterparts. Functional The online version of this article contains a data supplement.The publication co...

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Section: Self-renewal and Myeloid Commitment Capacitysupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34− cell population with intrinsic resistance to imatinib

Lemoli

Salvestrini

Bianchi

et al. 2009

Blood

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“…Real-time PCR also confirmed these data, revealing a key role for Pax7 in the early stages of GTPdependent myogenesis (at 4 h of differentiation). Among the genes involved in myogenesis, calcineurin (Ppp3ca) was up-regulated both at 4 and 24 h. Homeo box c4 regulates self-renewal and differentiation of stem cells, including both mesenchymal and embryonic stem cells [42]. The Rab17 gene was up-regulated, and it has been linked to the control of myogenesis, although it had never been identified and studied in skeletal muscle.…”

Section: Myogenesismentioning

confidence: 99%

Transcriptional profile of GTP-mediated differentiation of C2C12 skeletal muscle cells

Mancinelli

Pietrangelo

Burnstock³

et al. 2011

Purinergic Signalling

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Several purine receptors have been localised on skeletal muscle membranes. Previous data support the hypothesis that extracellular guanosine 5′-triphosphate (GTP) is an important regulatory factor in the development and function of muscle tissue. We have previously described specific extracellular binding sites for GTP on the plasma membrane of mouse skeletal muscle (C2C12) cells. Extracellular GTP induces an increase in intracellular Ca 2+ concentrations that results in membrane hyperpolarisation through Ca 2+ -activated K + channels, as has been demonstrated by patch-clamp experiments. This GTPevoked increase in intracellular Ca 2+ is due to release of Ca 2+ from intracellular inositol-1,4,5-trisphosphate-sensitive stores. This enhances the expression of the myosin heavy chain in these C2C12 myoblasts and commits them to fuse into multinucleated myotubes, probably via a phosphoinositide-3-kinase-dependent signal-transduction mechanism. To define the signalling of extracellular GTP as an enhancer or modulator of myogenesis, we investigated whether the gene-expression profile of differentiated C2C12 cells (4 and 24 h in culture) is affected by extracellular GTP. To investigate the nuclear activity and target genes modulated by GTP, transcriptional profile analysis and realtime PCR were used. We demonstrate that in the early stages of differentiation, GTP up-regulates genes involved in different pathways associated with myogenic processes, including cytoskeleton structure, the respiratory chain, myogenesis, chromatin reorganisation, cell adhesion, and the Jak/Stat pathway, and down-regulates the mitogenactivated protein kinase pathway. GTP also increases the expression of three genes involved in myogenesis, Pp3ca, Gsk3b, and Pax7. Our data suggests that in the myogenic C2C12 cell line, extracellular GTP acts as a differentiative factor in the induction and sustaining of myogenesis.

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“…17 In murine mesenchymal stem cells, Hoxb2, Hoxb5, Hoxb7, and Hoxc4 have been reported to regulate self-renewal. 18 Hox genes also regulate self-renewal/differentiation of hematopoietic stem cells (HSCs). During hematopoiesis, cells in distinct stages of differentiation have specific Hox gene expression profiles, and overexpression of Hox genes, such as Hoxb4, can reprogram cells to maintain a stem/progenitor state.…”

Section: Introductionmentioning

confidence: 99%

Hoxa3 promotes the differentiation of hematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells

Mahdipour

Charnock

Mace

2011

Blood

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Murine mesenchymal and embryonic stem cells express a similar Hox gene profile

Cited by 30 publications

References 29 publications

Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34− cell population with intrinsic resistance to imatinib

Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34− cell population with intrinsic resistance to imatinib

Transcriptional profile of GTP-mediated differentiation of C2C12 skeletal muscle cells

Hoxa3 promotes the differentiation of hematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells

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