Specification and function of hemogenic endothelium during embryogenesis

Gritz, Emily C.; Hirschi, Karen K.

doi:10.1007/s00018-016-2134-0

Cited by 98 publications

(94 citation statements)

References 219 publications

(312 reference statements)

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“…Analysis of miR-24 target genes revealed similar cell motility terms including sprouting angiogenesis and vascular cell migration, as well as contained chondroitin sulfate biosynthesis involved in cartilage production (Holmborn et al, 2012) (Figure 2G). In comparison, miR-223 target gene categories were often related to stem cell function such as hemangioblast cell differentiation, G1/S cell cycle transition, and cell shape regulation (Gritz and Hirschi, 2016) (Figure 2H). …”

Section: Resultsmentioning

confidence: 99%

MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos

et al. 2017

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SUMMARY Proper functioning of an organism requires cells and tissues to behave in uniform, well-organized ways. How this optimum of phenotypes is achieved during the development of vertebrates is unclear. Here, we carried out a multifaceted and single-cell resolution screen of zebrafish embryonic blood vessels upon mutagenesis of single and multi-gene miRNA families. We found that embryos lacking particular miRNA-dependent signaling pathways develop a vascular trait similar to wild type, but with a profound increase in phenotypic heterogeneity. Aberrant trait variance in miRNA mutant embryos uniquely sensitizes their vascular system to environmental perturbations. We discovered a previously unrecognized role for specific vertebrate miRNAs to protect tissue development against phenotypic variability. This discovery marks an important advance in our comprehension of how miRNAs function in the development of higher organisms.

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Section: Resultsmentioning

confidence: 99%

MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos

et al. 2017

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“…HSCs are rare hematopoietic cells sitting at the apex of the hematopoietic hierarchy, and possess extensive ability to self-renew as well as the capacity to gradually differentiate into downstream hematopoietic lineages. During fetal development, HSCs emerge as part of the definitive hematopoiesis program, best characterized through budding from special populations of endothelial cells [1, 4, 5]. Newly emerged HSCs migrate to and colonize the fetal liver, a stage that is accompanied by HSCs undergoing active cell cycle [4].…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs in Control of Stem Cells in Normal and Malignant Hematopoiesis

Roden

Lü

2016

Curr Stem Cell Rep

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Studies on hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) have helped to establish the paradigms of normal and cancer stem cell concepts. For both HSCs and LSCs, specific gene expression programs endowed by their epigenome functionally distinguish them from their differentiated progenies. MicroRNAs (miRNAs), as a class of small non-coding RNAs, act to control post-transcriptional gene expression. Research in the past decade has yielded exciting findings elucidating the roles of miRNAs in control of multiple facets of HSC and LSC biology. Here we review recent progresses on the functions of miRNAs in HSC emergence during development, HSC switch from a fetal/neonatal program to an adult program, HSC self-renewal and quiescence, HSC aging, HSC niche, and malignant stem cells. While multiple different miRNAs regulate a diverse array of targets, two common themes emerge in HSC and LSC biology: miRNA mediated regulation of epigenetic machinery and cell signaling pathways. In addition, we propose that miRNAs themselves behave like epigenetic regulators, as they possess key biochemical and biological properties that can provide both stability and alterability to the epigenetic program. Overall, the studies of miRNAs in stem cells in the hematologic contexts not only provide key understandings to post-transcriptional gene regulation mechanisms in HSCs and LSCs, but also will lend key insights for other stem cell fields.

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“…Endothelial to haemogenic endothelial cell and HSC transition (EHT) 21,22 is mediated by signals from niche cells 23–25 within the aorta-gonad-mesonephros region 26 during a narrow determine the pathways that drive this ontological process 27 . To this end, we devised a tractable stepwise approach whereby conditional expression of Fgrs in adult mouse endothelial cells co-cultured with an inductive vascular-niche converts adult endothelial cells into engraftable HSCs (rEC-HSCs) that possess all attributes of bona fide HSCs.…”

mentioning

confidence: 99%

Conversion of adult endothelium to immunocompetent haematopoietic stem cells

Lis

Karrasch

Poulos

et al. 2017

Nature

197

175

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Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully converting adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of genes encoding the transcription factors Fosb, Gfi1, Runx1, and Spi1 (also known as Fgrs) and vascular-niche-derived angiocrine factors. The induction phase (day 0–8) of conversion is initiated by expression of Fgrs in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (day 8–20), Runx1+ Fgrs-transduced endothelial cells commit to a haematopoietic fate yielding rEC-HSCs that no longer require Fgrs expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (at day 20–28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, are competent for clonal engraftment and serial primary and secondary multi-lineage reconstituting potential, including antigen-dependent adaptive immune function. Inhibition of TGF-β and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders.

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Specification and function of hemogenic endothelium during embryogenesis

Cited by 98 publications

References 219 publications

MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos

MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos

MicroRNAs in Control of Stem Cells in Normal and Malignant Hematopoiesis

Conversion of adult endothelium to immunocompetent haematopoietic stem cells

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