Murine hemogenic endothelial precursors display heterogeneous hematopoietic potential ex vivo

Ganuza, Miguel; Hadland, Brandon; Chabot, Ashley; Li, Chen; Kang, Guolian; Bernstein, Irwin D.; McKinney‐Freeman, Shannon

doi:10.1016/j.exphem.2017.04.006

Cited by 20 publications

(14 citation statements)

References 38 publications

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“…This indicates that only a limited number of EC in the PE are able to transform into cells having hemogenic potential. Such observation is consistent with quantitative evaluations, performed by other authors, for the HE found in various locations (Ganuza et al 2017). Our detecting of CD31/Runx1-double-positive cells may suggest the presence of the HE in the PE.…”

Section: Discussionsupporting

confidence: 93%

“…The variability of colonies grown from specific-cell-type populations isolated from the PE in our study may reflect the HE heterogeneity, which had been suggested by other authors (Ganuza et al 2017). …”

Section: Discussionsupporting

confidence: 69%

“…This specific EC subpopulation forms a transient cell type, which is estimated to constitute between 1 and 3% of the entire endothelial cell population in murine yolk sac and the aorta/gonad/mesonephros region (Gritz and Hirschi 2016). By means of clonal ex vivo assays (in which endothelial cells isolated from the mid-gestation aorta and vitelline and umbilical arteries were co-cultured on supportive stroma), it has been documented that only about 0.1% (9.5 dpc), 1.3% (10.5 dpc), and 0.29% (11.5 dpc) of the entire endothelium represents a functional hemogenic endothelium (Ganuza et al 2017). Here, we present the evidence that some EC of the PE also possess the hemogenic potential.…”

Section: Discussionmentioning

confidence: 99%

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Cells with hematopoietic potential reside within mouse proepicardium

Jankowska‐Steifer

Niderla-Bielińska

Ciszek

et al. 2018

Histochem Cell Biol

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During embryonic development, hematopoietic cells are present in areas of blood-vessel differentiation. These hematopoietic cells emerge from a specific subpopulation of endothelial cells called the hemogenic endothelium. We have previously found that mouse proepicardium contained its own population of endothelial cells forming a network of vascular tubules. We hypothesize that this EC population contains cells of hematopoietic potential. Therefore, we investigated an in vitro hematopoietic potential of proepicardial cell populations. The CD31+/CD45−/CD71− cell population cultured for 10 days in MethocultTM gave numerous colonies of CFU-GEMM, CFU-GM, and CFU-E type. These colonies consisted of various cell types. Flk-1+/CD31−/CD45−/CD71−, and CD45+ and/or CD71+ cell populations produced CFU-GEMM and CFU-GM, or CFU-GM and CFU-E colonies, respectively. Immunohistochemical evaluations of smears prepared from colonies revealed the presence of cells of different hematopoietic lineages. These cells were characterized by labeling with various combinations of antibodies directed against CD31, CD41, CD71, c-kit, Mpl, Fli1, Gata-2, and Zeb1 markers. Furthermore, we found that proepicardium-specific marker WT1 co-localized with Runx1 and Zeb1 and that single endothelial cells bearing CD31 molecule expressed Runx1 in the proepicardial area of embryonic tissue sections. We have shown that cells of endothelial and/or hematopoietic phenotypes isolated from mouse proepicardium possess hematopoietic potential in vitro and in situ. These results are supported by RT-PCR analyses of proepicardial extract, which revealed the expression of mRNA for crucial regulatory factors for hemogenic endothelium specification, i.e., Runx1, Notch1, Gata2, and Sox17. Our data are in line with previous observation on hemangioblast derivation from the quail PE.Electronic supplementary materialThe online version of this article (10.1007/s00418-018-1661-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cells with hematopoietic potential reside within mouse proepicardium

Jankowska‐Steifer

Niderla-Bielińska

Ciszek

et al. 2018

Histochem Cell Biol

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“… 34 Clonal output is also likely heterogenous, as recent work using limited dilutional analyses suggests, with increased heterogeneous HSPC populations at E10 vs. E11. 42 Thus, IAHC formation is likely driven by the rapid cell proliferation of several hemogenic endothelial clones with differing functional capacities. These findings further support a recent observation that an initial pool of pre-HSCs is established, from which HSCs mature from by E11.5.…”

Section: Discussionmentioning

confidence: 99%

Cell cycle dynamics and complement expression distinguishes mature haematopoietic subsets arising from hemogenic endothelium

et al. 2017

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The emergence of haematopoietic stem and progenitor cells (HSPCs) from hemogenic endothelium results in the formation of sizeable HSPC clusters attached to the vascular wall. We evaluate the cell cycle and proliferation of HSPCs involved in cluster formation, as well as the molecular signatures from their initial appearance to the point when cluster cells are capable of adult engraftment (definitive HSCs). We uncover a non-clonal origin of HSPC clusters with differing cell cycle, migration, and cell signaling attributes. In addition, we find that the complement cascade is highly enriched in mature HSPC clusters, possibly delineating a new role for this pathway in engraftment.

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“…This research collectively indicated that the appearance of cells having definitive HSC characteristics is in close association with arterial endothelium. Notably, umbilical arteries have been identified by a number of investigators as one of the primary birthplace of HSCs except the dorsal aorta in the aorta-gonad-mesonephros (AGM) region and the vitelline arteries [13,14], raising the possibility that arterial endothelial cells (AECs) within umbilical cord might harbor a complex network of signals to modulate the nascent HSCs. Interestingly, there is growing evidence that endothelium not only plays a fundamental role in the generation of definitive HSCs but also is essential for the self-renewal of HSCs in vitro or BM repopulation in vivo recently [15,16].…”

Section: Introductionmentioning

confidence: 99%

Arterial endothelium creates a permissive niche for expansion of human cord blood hematopoietic stem and progenitor cells

Li¹,

Pei

Wang³

et al. 2020

Stem Cell Res Ther

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Background: Although cord blood (CB) offers promise for treatment of patients with high-risk hematological malignancies and immune disorders, the limited numbers of hematopoietic stem cell (HSC)/progenitor cell in a CB unit and straitened circumstances in expanding ex vivo make it quite challenging to develop the successful cell therapies. Methods: In this study, a novel strategy has been developed to support ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) by coculture with engineered human umbilical arterial endothelial cells (HuAECs-E4orf1-GFP), which expresses E4ORF1 stably by using a retroviral system. Results: Coculture of CD34 + hCB cells with HuAECs-E4orf1-GFP resulted in generation of considerably more total nucleated cells, CD34 + CD38 − , and CD34 + CD38 − CD90 + HSPCs in comparison with that of cytokines alone or that of coculture with human umbilical vein endothelial cells (HuVECs) after 14-day amplification. The in vitro multilineage differentiation potential and in vivo repopulating capacity of the expanded hematopoietic cells cocultured with HuAECs-E4orf1-GFP were also markedly enhanced compared with the other two control groups. DLL4, a major determinant of arterial endothelial cell (EC) identity, was associated with CD34 + hCB cells amplified on HuAECs-E4orf1-GFP. Conclusions: Collectively, we demonstrated that HuAECs acted as a permissive niche in facilitating expansion of HSPCs. Our study further implicated that the crucial factors and related pathways presented in HuAECs may give a hint to maintain self-renewal of bona fide HSCs.

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Murine hemogenic endothelial precursors display heterogeneous hematopoietic potential ex vivo

Cited by 20 publications

References 38 publications

Cells with hematopoietic potential reside within mouse proepicardium

Cells with hematopoietic potential reside within mouse proepicardium

Cell cycle dynamics and complement expression distinguishes mature haematopoietic subsets arising from hemogenic endothelium

Arterial endothelium creates a permissive niche for expansion of human cord blood hematopoietic stem and progenitor cells

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