Identification of Cdca7 as a novel Notch transcriptional target involved in hematopoietic stem cell emergence

Guiu, Jordi; Bergen, Dylan J. M.; Pater, Emma de; Islam, Abul B.M.M.K.; Ayllón, Verónica; Gama-Norton, Leonor; Ruiz-Herguido, Cristina; González, Jéssica; López‐Bigas, Núria; Menéndez, Pablo; Dzierzak, Elaine; Espinosa, Lluís; Bigas, Anna

doi:10.1084/jem.20131857

Cited by 51 publications

(23 citation statements)

References 55 publications

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“…1e , Supplementary Table 1 ). CDCA7 is involved in neoplastic transformation, MYC -dependent apoptosis and haematopoietic stem cell emergence; however, its molecular function is unknown 13 14 . All four zinc-finger motifs are completely conserved in the highly homologous 4-CXXC zinc-finger domain of the transcriptional repressor CDCA7-Like ( CDCA7L ; Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Mutations in CDCA7 and HELLS cause immunodeficiency–centromeric instability–facial anomalies syndrome

et al. 2015

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The life-threatening Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome is a genetically heterogeneous autosomal recessive disorder. Twenty percent of patients cannot be explained by mutations in the known ICF genes DNA methyltransferase 3B or zinc-finger and BTB domain containing 24. Here we report mutations in the cell division cycle associated 7 and the helicase, lymphoid-specific genes in 10 unexplained ICF cases. Our data highlight the genetic heterogeneity of ICF syndrome; however, they provide evidence that all genes act in common or converging pathways leading to the ICF phenotype.

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Section: Resultsmentioning

confidence: 99%

Mutations in CDCA7 and HELLS cause immunodeficiency–centromeric instability–facial anomalies syndrome

et al. 2015

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“…The Runx1 and Gata2 transcription factors also show expression in the ventral aspect of the aorta at E10.5 and are required for hematopoietic progenitor and stem cell generation from hemogenic endothelium (Chen et al, 2009; Tober et al, 2013). Moreover, Notch signalling is essential for EHT in vivo (Gama-Norton et al, 2015), initiating endothelial cell fate change to a hematopoietic cell in the AGM through the Notch ligand jagged 1 (Robert-Moreno et al, 2008; Gerhardt et al, 2014; Guiu et al, 2014; Tang et al, 2013). Notch 1 is expressed in most of the cells of the intra-aortic hematopoietic clusters, similar to jagged 1 (Robert-Moreno et al, 2008).…”

Section: Exploring the Possible Origins Of Hsc Heterogeneitymentioning

confidence: 99%

The many faces of hematopoietic stem cell heterogeneity

Crisan

Dzierzak

2016

Development

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Not all hematopoietic stem cells (HSCs) are alike. They differ in their physical characteristics such as cell cycle status and cell surface marker phenotype, they respond to different extrinsic signals, and they have different lineage outputs following transplantation. The growing body of evidence that supports heterogeneity within HSCs, which constitute the most robust cell fraction at the foundation of the adult hematopoietic system, is currently of great interest and raises questions as to why HSC subtypes exist, how they are generated and whether HSC heterogeneity affects leukemogenesis or treatment options. This Review provides a developmental overview of HSC subtypes during embryonic, fetal and adult stages of hematopoiesis and discusses the possible origins and consequences of HSC heterogeneity.

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“…CDCA7 expression was shown to be upregulated in the hemogenic population derived from human embryonic stem cells in a Notch-dependent manner. Down-regulation of Cdca7 mRNA was shown to induce hematopoietic differentiation and concomitantly decrease HSPC numbers, suggesting that it is a Notch-mediated target involved in emergence of HSPC, but not differentiation of these cells [ 175 ].…”

Section: Generation Of Hematopoietic Stem/progenitor Cells From Hemogmentioning

confidence: 99%

Specification and function of hemogenic endothelium during embryogenesis

Gritz

Hirschi

2016

Cell. Mol. Life Sci.

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Hemogenic endothelium is a specialized subset of developing vascular endothelium that acquires hematopoietic potential and can give rise to multilineage hematopoietic stem and progenitor cells during a narrow developmental window in tissues such as the extraembryonic yolk sac and embryonic aorta-gonad-mesonephros. Herein, we review current knowledge about the historical and developmental origins of hemogenic endothelium, the molecular events that govern hemogenic specification of vascular endothelial cells, the generation of multilineage hematopoietic stem and progenitor cells from hemogenic endothelium, and the potential for translational applications of knowledge gained from further study of these processes.

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Identification of Cdca7 as a novel Notch transcriptional target involved in hematopoietic stem cell emergence

Cited by 51 publications

References 55 publications

Mutations in CDCA7 and HELLS cause immunodeficiency–centromeric instability–facial anomalies syndrome

Mutations in CDCA7 and HELLS cause immunodeficiency–centromeric instability–facial anomalies syndrome

The many faces of hematopoietic stem cell heterogeneity

Specification and function of hemogenic endothelium during embryogenesis

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