Progenitor analysis of primitive erythropoiesis generated from in vitro culture of embryonic stem cells

Otani, Takeshi; Inoue, Toshiya; Tsuji-Takayama, Kazue; Ijiri, Yoshihiro; Nakamura, Shuji; Motoda, Ryuichi; Orita, Kunzo

doi:10.1016/j.exphem.2005.03.006

Cited by 16 publications

(8 citation statements)

References 41 publications

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“…Genetic deletion of Flk1 results in endothelial but not primitive hematopoietic impairment in chimeric mice (Shalaby et al, 1997). However, subsequent studies in stromal cocultures determined that Flk1 delivers important instructive cues to generate normal hematopoietic progenitors (Hidaka et al, 1999), and controls fate decisions through differential cell surface expression of CD41 (Otani et al, 2005). VEGF confers dose-dependent survival to primitive progenitors (Martin et al, 2004), and FLK1 marks primitive streak mesoderm predictive of hematopoietic potential (Era et al, 2008).…”

Section: The Next Step: How Observations In Yolk Sac Hematopoiesis Camentioning

confidence: 99%

Modeling murine yolk sac hematopoiesis with embryonic stem cell culture systems

Cook

2014

Front. Biol.

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The onset of hematopoiesis in mammals is defined by generation of primitive erythrocytes and macrophage progenitors in embryonic yolk sac. Laboratories have met the challenge of transient and swiftly changing specification events from ventral mesoderm through multipotent progenitors and maturing lineage-restricted hematopoietic subtypes, by developing powerful in vitro experimental models to interrogate hematopoietic ontogeny. Most importantly, studies of differentiating embryonic stem cell derivatives in embryoid body and stromal coculture systems have identified crucial roles for transcription factor networks (e.g. Gata1, Runx1, Scl) and signaling pathways (e.g. BMP, VEGF, WNT) in controlling stem and progenitor cell output. These and other relevant pathways have pleiotropic biological effects, and are often associated with early embryonic lethality in knockout mice. Further refinement in subsequent studies has allowed conditional expression of key regulatory genes, and isolation of progenitors via cell surface markers (e.g. FLK1) and reporter-tagged constructs, with the purpose of measuring their primitive and definitive hematopoietic potential. These observations continue to inform attempts to direct the differentiation, and augment the expansion, of progenitors in human cell culture systems that may prove useful in cell replacement therapies for hematopoietic deficiencies. The purpose of this review is to survey the extant literature on the use of differentiating murine embryonic stem cells in culture to model the developmental process of yolk sac hematopoiesis.

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Section: The Next Step: How Observations In Yolk Sac Hematopoiesis Camentioning

confidence: 99%

Modeling murine yolk sac hematopoiesis with embryonic stem cell culture systems

Cook

2014

Front. Biol.

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“…CD41a + cells were detected 1 d later within the CD235a + population. The sequence of appearance of erythroid markers and CD41a in differentiating human ESCs was different from differentiating mouse ESCs, where expression of CD41a preceded the expression of TER119 erythroid marker 45 , 46 . The first cells expressing hematopoietic markers, i.e., VE-cadherin + CD73 − CD235a + CD43 low CD41a − phenotype, had unique functional properties (see Table 1).…”

Section: Identification Of Hierarchy Of Angiohematopoietic Progenitormentioning

confidence: 99%

Deciphering the hierarchy of angiohematopoietic progenitors from human pluripotent stem cells

Slukvin

2013

Cell Cycle

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Identification of sequential progenitors leading to blood formation from pluripotent stem cells (PSCs) will be essential for understanding the molecular mechanisms of hematopoietic lineage specification and for development of technologies for in vitro production of hematopoietic stem cells (HSCs). It is well established that during development, blood and endothelial cells in the extraembryonic and embryonic compartments are formed in parallel from precursors with angiogenic and hematopoietic potentials. However, the identity and hierarchy of these precursors in human PSC (hPSC) cultures remain obscure. Using developmental stage-specific mesodermal and endothelial markers and functional assays, we recently identified discrete populations of angiohematopoietic progenitors from hPSCs, including mesodermal precursors and hemogenic endothelial cells with primitive and definitive hematopoietic potentials. In addition, we discovered a novel population of multipotent hematopoietic progenitors with an erythroid phenotype, which retain angiogenic potential. Here we introduce our recent findings and discuss their implication for defining putative HSC precursor and factors required for activation of self-renewal potential in hematopoietic cells emerging from endothelium.

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“…Nevertheless, there have been some success in circumventing this limitation by inserting reporter genes into lineage-specific gene loci [10]–[15], or selecting for surface receptors known to be important in early tissue development e.g. Flk-1 in hematopoiesis and vasculogenesis [16]–[18]. However, CD73+ human mesenchymal stem cell population is, to date, the only lineage-restricted stem cell population to be prospectively isolated from ESC by markers and propagated as a self-renewing population in culture[18].…”

Section: Introductionmentioning

confidence: 99%

Establishing Clonal Cell Lines with Endothelial-Like Potential from CD9hi, SSEA-1− Cells in Embryonic Stem Cell-Derived Embryoid Bodies

et al. 2006

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BackgroundDifferentiation of embryonic stem cells (ESCs) into specific cell types with minimal risk of teratoma formation could be efficiently directed by first reducing the differentiation potential of ESCs through the generation of clonal, self-renewing lineage-restricted stem cell lines. Efforts to isolate these stem cells are, however, mired in an impasse where the lack of purified lineage-restricted stem cells has hindered the identification of defining markers for these rare stem cells and, in turn, their isolation.Methodology/Principal FindingsWe describe here a method for the isolation of clonal lineage-restricted cell lines with endothelial potential from ESCs through a combination of empirical and rational evidence-based methods. Using an empirical protocol that we have previously developed to generate embryo-derived RoSH lines with endothelial potential, we first generated E-RoSH lines from mouse ESC-derived embryoid bodies (EBs). Despite originating from different mouse strains, RoSH and E- RoSH lines have similar gene expression profiles (r2 = 0.93) while that between E-RoSH and ESCs was 0.83. In silico gene expression analysis predicted that like RoSH cells, E-RoSH cells have an increased propensity to differentiate into vasculature. Unlike their parental ESCs, E-RoSH cells did not form teratomas and differentiate efficiently into endothelial-like cells in vivo and in vitro. Gene expression and FACS analysis revealed that RoSH and E-RoSH cells are CD9hi, SSEA-1− while ESCs are CD9lo, SSEA-1+. Isolation of CD9hi, SSEA-1− cells that constituted 1%–10% of EB-derived cultures generated an E-RoSH-like culture with an identical E-RoSH-like gene expression profile (r2 = 0.95) and a propensity to differentiate into endothelial-like cells.ConclusionsBy combining empirical and rational evidence-based methods, we identified definitive selectable surface antigens for the isolation and propagation of lineage-restricted stem cells with endothelial-like potential from mouse ESCs.

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Progenitor analysis of primitive erythropoiesis generated from in vitro culture of embryonic stem cells

Cited by 16 publications

References 41 publications

Modeling murine yolk sac hematopoiesis with embryonic stem cell culture systems

Modeling murine yolk sac hematopoiesis with embryonic stem cell culture systems

Deciphering the hierarchy of angiohematopoietic progenitors from human pluripotent stem cells

Establishing Clonal Cell Lines with Endothelial-Like Potential from CD9hi, SSEA-1− Cells in Embryonic Stem Cell-Derived Embryoid Bodies

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