Cellular and molecular biology of megakaryocyte differentiation in the absence of lineage&amp;hyphen;restricted transcription factors

Lécine, Patrick; Shivdasani, Ramesh A.

doi:10.1002/stem.5530160712

Cited by 8 publications

(7 citation statements)

References 23 publications

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“…In fact, they expressed consistently more Gata1, Gata2, MITF, and MMCP-6 (early marker 38 ) but less MC-CPA (a serosal maturation marker 39 ) than the corresponding wild-type cells ( Figure 2D). Interestingly, these cells expressed NFE2, a gene involved in the control of megakaryocytic-erythroid, rather than mastocytic, differentiation 40 ( Figure 2D). BMMCs from all the mice groups investigated were capable of incorporating and releasing serotonin after IgE-␣IgE stimulation already by day 7 18,21 The myeloid generating cells are divided by CD34 and CD16/CD32 staining into GMPs (CD34 ϩ CD16/CD32 ϩ , not shown), MEPs (CD34 low CD16/CD32 low ), and CMPs (CD34 ϩ CD16/CD32 low ).…”

Section: Resultsmentioning

confidence: 99%

The hypomorphic Gata1low mutation alters the proliferation/differentiation potential of the common megakaryocytic-erythroid progenitor

Ghinassi

Sanchez

Martelli

et al. 2006

Blood

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Recent evidence suggests that mutations in the IntroductionAmong the GATA family of transcription factors, 1 Gata1 exerts a specific role in the control of erythroid, 2 megakaryocytic, 3,4 eosinophil, 5 and mast 6 cell differentiation. Genetic alterations of this gene, however, are not only associated with X-linked inherited erythroid or megakaryocytic disorders, but are also found in acquired myeloproliferative disorders. Each mutation is associated with a specific abnormality: point mutations that abrogate the ability of the amino-terminal zinc finger domain of the protein to bind either DNA or Fog1, a partner of Gata1, are found in inherited disorders. [7][8][9][10] On the other hand, frame shift and splice mutations encoding GATA1s, a protein lacking the amino-terminal domain, are associated not only with impaired inherited erythropoiesis, 11,12 but are also found in patients with megakaryocytic leukemia in Down syndrome, 13,14 in newborns with transient myeloproliferative syndromes, 15 and in one adult patient with megakaryocytic leukemia. 16 These observations suggest that, in addition to its effect on terminal differentiation, Gata1 might control the biologic properties of hematopoietic progenitor cells, predisposing them to accumulate secondary mutations in a multistep leukemogenic process. However, direct proof for a possible function of Gata1 in progenitor cells has not been provided as yet.We had previously described that hematopoietic tissues from mice carrying the hypomorphic Gata1 low mutation contain high numbers (ϳ10%) of "unique" progenitor cells that generate colonies composed of erythroblasts, megakaryocytes, and mast cells. 6 Predicted by the stochastic model of hematopoietic commitment, 17 such a trilineage progenitor has not been isolated prospectively as yet from the marrow of normal mice. In fact, antigenic profiling has prospectively divided normal murine progenitors into myeloid-and mast cell-restricted. The myeloid-restricted ones are further divided into granulomonocytic progenitors (GMPs), megakaryocytic-erythroid progenitors (MEPs), and common myeloid progenitors (CMPs). 18 GMPs correspond to cells previously defined, by functional clonogenesis, as colony-forming cells that generate in 7 days granulocytic, monomacrophagic and granulomonocytic colonies (CFU-Gs, CFU-Ms, and CFU-GMs). MEPs, on the other hand, include cells once functionally defined as those that generate megakaryocytic or erythroid colonies either in 3 days (CFU-MKs day3 and CFU-Es) or 7 days (CFU-MKs day7 and BFUEs). CMPs were functionally defined as multilineage progenitor cells, that is, those that generate colonies of multiple lineages after 12 to 15 days either in vitro (CFU-mix) or in vivo (spleen colony-forming cells, CFU-Ss day12 ). Mast cells are localized in extramedullary sites where they engage themselves in the process of allergic response and in the immune reaction against parasites. 19,20 As all the other hematopoietic cells, they derive from progenitor cells present in the marrow (and in the spleen) of ...

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Section: Resultsmentioning

confidence: 99%

The hypomorphic Gata1low mutation alters the proliferation/differentiation potential of the common megakaryocytic-erythroid progenitor

Ghinassi

Sanchez

Martelli

et al. 2006

Blood

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“…The duplicated copies constitute welldefined gene families whose members may be clustered together (histones, rRNA, globins, immunoglobins, and MHC) or dispersed on different chromosomes (or a combination of both). Almost all the genes (including those that encode for transcription factors) are members of families, such as zinc finger (Nagaoka and Sugiura, 2000;Lecine and Shivdasani, 1998;Beyersmannn, 2000;Wolfe et al, 2000); bHLH (Fritzsch et al, 2000;Norton, 2000;Kageyama et al, 2000), or homeobox genes (Kappen, 2000;Coulier et al, 2000;Gibson, 2000). In the genome, these families are organized in different chromosomal location rather than being clustered on a single chromosome (Alonso and Cabrera, 1988;Knust et al, 1992).…”

Section: Introductionmentioning

confidence: 94%

Cross-Species Conservation of SEL1L, a Human Pancreas–Specific Expressing Gene

Biunno

Castiglioni

Rogozin

et al. 2002

OMICS: A Journal of Integrative Biology

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SEL1L is a recently cloned and organ-specific expressing human gene whose function is still at an embryonic stage but displays several interesting characteristics, among which a remarkable cross-species conservation. During evolution, the gene structural complexity increased, suggesting a diversification of its function; however, several amino acid motifs remain perfectly conserved from the bacteria to the human protein. SEL1L is the human ortholog of the C. elegans gene sel-1; the latter is implicated in the negative regulation of LIN-12/GLP-1/Notch receptor proteins. These receptor proteins play fundamental roles in signal transduction pathways and are key players in cell fate determination during the development of various organs. Studies in model organisms, such as C. elegans, helped to illuminate fundamental mechanisms involved in normal cellular functions and human diseases. This paper describes the conserved nature of SEL1L across a wide range of species suggesting, that the encoded protein most likely exerts a very important biological function; it may belong to a subclass of genes considered to be "essential."

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“…Nuclear factor erythroid 2 (NF-E2) is a heterodimeric leucine zipper TF that comprises an MK-erythroid specific 45-kDa subunit and a non-lineage specific p18 Maf family subunit which controls terminal MK maturation, proplatelet formation and platelet release (Lecine & Shivdasani, 1998;, by regulating a panoply of MK genes which are crucial elements in the process of platelet production. Little is known about disorders of human platelet production; however, Maf or P45 mutations in mice result in severe impairment of megakaryocytopoiesis (Onodera et al, 2000).…”

Section: Nuclear Transcription Factorsmentioning

confidence: 99%

Megakaryocyte development and platelet production

2006

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SummaryMegakaryocytopoiesis involves the commitment of haematopoietic stem cells, and the proliferation, maturation and terminal differentiation of the megakaryocytic progenitors. Circulating levels of thrombopoietin (TPO), the primary growth-factor for the megakaryocyte (MK) lineage, induce concentration-dependent proliferation and maturation of MK progenitors by binding to the c-Mpl receptor and signalling induction. Decreased platelet turnover rates results in increased concentration of free TPO, enabling the compensatory response of marrow MKs to increased platelet production. C-Mpl activity is orchestrated by a complex cascade of signalling molecules that induces the action of specific transcription factors to drive MK proliferation and maturation. Mature MKs form proplatelet projections that are fragmented into circulating particles. Newly developed thrombopoietic agents operating via c-Mpl receptor may prove useful in supporting platelet production in thrombocytopenic state. Herein, we review the regulation of megakaryocytopoiesis and platelet production in normal and disease state, and the new approaches to thrombopoietic therapy.

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Cellular and molecular biology of megakaryocyte differentiation in the absence of lineage&hyphen;restricted transcription factors

Cited by 8 publications

References 23 publications

The hypomorphic Gata1low mutation alters the proliferation/differentiation potential of the common megakaryocytic-erythroid progenitor

The hypomorphic Gata1low mutation alters the proliferation/differentiation potential of the common megakaryocytic-erythroid progenitor

Cross-Species Conservation of SEL1L, a Human Pancreas–Specific Expressing Gene

Megakaryocyte development and platelet production

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