The notch pathway positively regulates programmed cell death during erythroid differentiation

Robert‐Moreno, Alexandre; Espinosa, Lluís; Sánchez, María José; Pompa, José Luis de la; Bigas, Anna

doi:10.1038/sj.leu.2404705

Cited by 48 publications

(53 citation statements)

References 49 publications

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“…Around E9, several types of myeloid and erythroid progenitors are detected in both the embryo and the yolk sac, and it is also around this time that the first stem cell activity is detected in the embryo and yolk sac by transplantation of busulphan-conditioned new-born mice (Yoder et al, 1997). Interestingly, only this second wave of definitive hematopoiesis is abrogated in the Notch mutant embryos, including Notch1, RBPjκ/CSL or Jagged1 knockouts and the stem cell activity is completely lost in the Notch1 mutant embryos Robert-Moreno et al, 2007;Robert-Moreno et al, 2008). Together this data supports the idea that there are two well-differentiated genetic programs responsible for embryonic hematopoiesis, being one Notch-dependent and the other Notchindependent.…”

Section: Notch Mutant Phenotypes In Embryonic Hematopoiesis: the Yolksupporting

confidence: 59%

“…As previously mentioned, pre-and post-circulation hematopoiesis in the yolk sac of RBPjκ/CSL null embryos is apparently normal (Robert-Moreno et al, 2007). Nevertheless, when we analyzed the erythroid Ter119 + cells in the blood islands of the RBPjκ null yolk sacs, we found an increase in the percentage and number of these cells that was attributed to reduced apoptosis.…”

Section: Notch Signaling Modulates Red Cell Homeostasis In the Yolk Sacmentioning

confidence: 48%

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The Notch pathway in the developing hematopoietic system

Bigas

Robert‐Moreno²,

Espinosa³

2010

Int. J. Dev. Biol.

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The main function of the Notch signaling pathway is to generate cell diversity during both embryonic development and adult tissue homeostasis. The extended use of this pathway, together with its conservation during evolution, is indicative of its importance. During embryonic development, the vascular and hematopoietic systems are intimately associated and Notch signals are responsible for the correct specification of both systems. More explicitly, Notch is required for the induction of the arterial program; however, it is simultaneously or consecutively also involved in the generation of hematopoietic stem cells. Although both genetic programs are different, they are both implemented in endothelial cells of the dorsal aorta in the midgestation embryo. This close association during the development of arteries and blood has hindered our understanding of Notch function in the generation of hematopoietic stem cells. Here, we will review the work from recent years showing how Notch participates in the embryonic development of hematopoiesis in the mouse, but also in other organisms such as chick, zebrafish and flies.

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Section: Notch Mutant Phenotypes In Embryonic Hematopoiesis: the Yolksupporting

confidence: 59%

Section: Notch Signaling Modulates Red Cell Homeostasis In the Yolk Sacmentioning

confidence: 48%

The Notch pathway in the developing hematopoietic system

Bigas

Robert‐Moreno²,

Espinosa³

2010

Int. J. Dev. Biol.

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“…Notch in myeloid/erythroid differentiation It has been shown that Notch1/RBP-J positively regulates apoptosis during erythroid development [146]. However, its role in myelopoiesis remains unclear and controversial.…”

Section: Notch and B-cell Developmentmentioning

confidence: 99%

The Notch signaling pathway: Transcriptional regulation at Notch target genes

Borggrefe

Oswald

2009

Cell. Mol. Life Sci.

574

499

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. The Notch gene encodes a transmembrane receptor that gave the name to the evolutionary highly conserved Notch signaling cascade. It plays a pivotal role in the regulation of many fundamental cellular processes such as proliferation, stem cell maintenance and differentiation during embryonic and adult development. After specific ligand binding, the intracellular part of the Notch receptor is cleaved off and translocates to the nucleus, where it binds to the transcription factor RBP-J. In the absence of activated Notch, RBP-J represses Notch target genes by recruiting a corepressor complex. Here, we review Notch signaling with a focus on gene regulatory events at Notch target genes. This is of utmost importance to understand Notch signaling since certain RBP-J associated cofactors and particular epigenetic marks determine the specificity of Notch target gene expression in different cell types. We subsequently summarize the current knowledge about Notch target genes and the physiological significance of Notch signaling in development and cancer.

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“…[22][23][24][25] Targeted inactivation of the Notch signaling components Notch1, RPBJk, Jag1 and Mib1 showed that Notch is essential for definitive hematopoiesis in the intraembryonic P-Sp/AGM region. 26,27 The tyrosine kinase receptor-2 (Tie2) is expressed on vascular endothelium and on HSCs, and Tie2 þ cells contain hemangioblasts able to differentiate into hematopoietic and endothelial lineages. 28 Since both Tie2 and Notch1 intracellular domain (N1ICD) proteins have similar expression patterns very early in the YS blood island, 29,30 we have used the Tie2-Cre driver line 31 to overexpress Notch1 (N1ICD-EGFP (enhanced green fluorescence protein)).…”

mentioning

confidence: 99%

Notch1 regulates progenitor cell proliferation and differentiation during mouse yolk sac hematopoiesis

et al. 2014

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Loss-of-function studies have demonstrated the essential role of Notch in definitive embryonic mouse hematopoiesis. We report here the consequences of Notch gain-of-function in mouse embryo hematopoiesis, achieved by constitutive expression of Notch1 intracellular domain (N1ICD) in angiopoietin receptor tyrosine kinase receptor-2 (Tie2)-derived enhanced green fluorescence protein (EGFP þ ) hematovascular progenitors. At E9.5, N1ICD expression led to the absence of the dorsal aorta hematopoietic clusters and of definitive hematopoiesis. The EGFP þ transient multipotent progenitors, purified from E9.5 to 10.5 Tie2-Cre;N1ICD yolk sac (YS) cells, had strongly reduced hematopoietic potential, whereas they had increased numbers of hemogenic endothelial cells. Late erythroid cell differentiation stages and mature myeloid cells (Gr1 þ , MPO þ ) were also strongly decreased. In contrast, EGFP þ erythro-myeloid progenitors, immature and intermediate differentiation stages of YS erythroid and myeloid cell lineages, were expanded. Tie2-Cre;N1ICD YS had reduced numbers of CD41 þ þ megakaryocytes, and these produced reduced below-normal numbers of immature colonies in vitro and their terminal differentiation was blocked. Cells from Tie2-Cre;N1ICD YS had a higher proliferation rate and lower apoptosis than wild-type (WT) YS cells. Quantitative gene expression analysis of FACS-purified EGFP þ YS progenitors revealed upregulation of Notch1-related genes and alterations in genes involved in hematopoietic differentiation. These results represent the first in vivo evidence of a role for Notch signaling in YS transient definitive hematopoiesis. Our results show that constitutive Notch1 activation in Tie2 þ cells hampers YS hematopoiesis of E9.5 embryos and demonstrate that Notch signaling regulates this process by balancing the proliferation and differentiation dynamics of lineage-restricted intermediate progenitors.

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The notch pathway positively regulates programmed cell death during erythroid differentiation

Cited by 48 publications

References 49 publications

The Notch pathway in the developing hematopoietic system

The Notch pathway in the developing hematopoietic system

The Notch signaling pathway: Transcriptional regulation at Notch target genes

Notch1 regulates progenitor cell proliferation and differentiation during mouse yolk sac hematopoiesis

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