Hematopoietic Progenitor Cells Derived from Embryonic Stem Cells: Analysis of Gene Expression

Lu, Shi‐Jiang; Quan, Chengshi; Li, Fēi; Vida, Loyda N.; Honig, George R.

doi:10.1634/stemcells.20-5-428

Cited by 22 publications

(17 citation statements)

References 40 publications

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“…In this regard, dedifferentiated structures have also been implicated as developmentally plastic transitional structures that serve to direct cell expansion and tissue differentiation in numerous species 71,72 including humans. 73 In keeping with these previous findings, the switch from islet to DEC is associated with upregulated expression of markers associated with stemness [48][49][50][51][52] including CD34, ABCG2, a-fetoprotein, b-galactosidase, PYY, nestin and NGN-3. Stocum has introduced the concept of regeneration competence 46 to describe adult cells that can be induced to regenerate the body's own tissues.…”

Section: Discussionsupporting

confidence: 78%

Morphogenetic plasticity of adult human pancreatic islets of Langerhans

Lipsett

Sladek

et al. 2005

Cell Death Differ

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The aim of this study was to investigate the phenotypic plasticity of pancreatic islets of Langerhans. Quiescent adult human islets were induced to undergo a phenotypic switch to highly proliferative duct-like structures in a process characterized by a loss of expression of islet-specific hormones and transcription factors as well as a temporally related rise in the expression of markers of both duct epithelial and progenitor cells. Short-term treatment of these primitive duct-like structures with the neogenic factor islet neogenesisassociated protein ) induced their reconversion back to islet-like structures in a PI3-kinase-dependent manner. These neoislets resembled freshly isolated human islets with respect to the presence and topological arrangement of the four endocrine cell types, islet gene expression and hormone production, insulin content and glucoseresponsive insulin secretion. Our results suggest that adult human islets possess a remarkable degree of morphogenetic plasticity. This novel observation may have important implications for understanding pancreatic carcinogenesis and islet neogenesis.

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Section: Discussionsupporting

confidence: 78%

Morphogenetic plasticity of adult human pancreatic islets of Langerhans

Lipsett

Sladek

et al. 2005

Cell Death Differ

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“…Therefore, in vitro and in vivo studies of primate hematopoietic development should be performed using primate-derived materials. In recent studies in primate ES cells, Kaufman et al and Li et al the coexistence of primitive and definitive hematopoiesis is recapitulated at the mRNA level (Lu et al, 2002). In this study, we have demonstrated for the first time the transition from primitive to definitive hematopoietic development in primate ES cells at both the transcriptional and the translational level in vitro.…”

Section: Discussionsupporting

confidence: 65%

“…Therefore, their ES cells might be used as a model for elucidating primate hematopoietic development. Recently primate ES cell lines were established (Thomson et al, 1995;Thomson et al, 1996;Thomson et al, 1998;Suemori et al, 2001), and hematopoietic differentiation from primate ES cells was also induced successfully in vitro (Kaufman et al, 2001;Li et al, 2001;Lu et al, 2002;Chadwick et al, 2003). However, compared with the murine system, little work has been done to precisely analyze primitive and definitive hematopoietic development.…”

Section: Introductionmentioning

confidence: 99%

Development of primitive and definitive hematopoiesis from nonhuman primate embryonic stem cells in vitro

et al. 2004

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Although information about the development of primitive and definitive hematopoiesis has been elucidated in murine embryos and embryonic stem (ES)cells, there have been few in vitro studies of these processes in primates. In this study, we investigated hematopoietic differentiation from cynomolgus monkey ES cells grown on OP9, a stromal cell line deficient in macrophage colony-stimulating factor. Primitive erythrocytes (EryP) and definitive erythrocytes (EryD) developed sequentially from ES cells in the culture system; this was confirmed by immunostaining and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of embryonic, fetal and adult globin genes. EryP were detected on day 8 without exogenous erythropoietin (EPO), whereas EryD appeared on day 16 and had an indispensable requirement for exogenous EPO. RT-PCR analysis of the cultures revealed a sequential expression of genes associated with primitive and definitive hematopoietic development that was equivalent to that seen during primate ontogeny in vivo. Vascular endothelial growth factor (VEGF) increased, in a dose-dependent manner, not only the number of floating hematopoietic cells,but also the number of adherent hematopoietic cell clusters containing CD34-positive immature progenitors. In colony assays, exogenous VEGF also had a dose-dependent stimulatory effect on the generation of primitive erythroid colonies. More efficient primitive and definitive erythropoiesis was induced by re-plating sorted CD34-positive cells. Thus, this system reproduces early hematopoietic development in vitro and can serve as a model for analyzing the mechanisms of hematopoietic development in primates.

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“…Studies on in vitro differentiating mouse ESCs have shown that erythropoietic differentiation within EBs recapitulates the transition from the primitive to the definitive lineages, 42,43 as defined by a switch from embryonic () to adult (␤) globin expression, respectively. To further characterize the erythroid subsets emerging from both control and VEGF-A 165 -treated EBs in the human, we assessed the transcriptional status of the embryonic and adult globin genes.…”

Section: Vegf-a 165 Enhances the Expression Of Both The Embryonic Andmentioning

confidence: 99%

VEGF-A165 augments erythropoietic development from human embryonic stem cells

Cerdan

Rouleau

Bhatia

2004

Blood

144

103

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IntroductionVascular endothelial growth factor (VEGF-A 165 ) is a multifunctional cytokine that plays a prominent role in normal vascular biology by regulating numerous cellular responses of endothelial precursors including proliferation, differentiation, migration, and apoptosis. [1][2][3][4][5][6] In addition, a role for VEGF-A 165 in hematopoietic differentiation has been identified, 7-10 and has been extended to primitive hematopoietic cells capable of repopulation from mouse embryonic stem cells (ESCs), 11 and by targeted gene disruption of VEGF-A 165 or its tyrosine kinase receptor VEGFR2/KDR/Flk-1 (hereafter KDR). 12-14 Furthermore, a role for VEGF-A 165 in early developmental events of primitive and definitive erythroid lineages from mouse ESCs has been established. 15 This latter observation indicates a potential function of VEGF-A 165 in cellular events leading to the emergence of mouse hematopoiesis that specifically affects erythroid differentiation.During mammalian embryogenesis, erythropoiesis occurs in 2 waves: the primitive wave, which occurs and remains confined to the extra-embryonic yolk sac, 16-18 is followed by the definitive wave, which originates in the yolk sac and/or within the embryo proper, 19,20 which then sequentially migrates to the fetal liver and ultimately to the bone marrow. 18 Definitive and primitive erythroid cells derived from mouse ESCs are morphologically distinct 9,21 and can be molecularly distinguished by differences in globin expression, where primitive erythroid cells express the embryonic and ⑀ globins whereas definitive cells express the adult ␤ globin. [22][23][24][25] Mammalian erythropoiesis from uncommitted pluripotent stem cells is an early cellular differentiation event that can be characterized by sequential progress through stages of progenitor development that can be assayed from erythroid blast-forming units (BFU-Es) to erythroid colony-forming units (CFU-Es) and eventually maturation into erythroblasts, normoblasts, reticulocytes, and finally enucleated mature erythrocytes. 26 This complex process is controlled by the combined effects of growth factors, including the erythroid-specific cytokine erythropoietin (EPO). 27 Because human embryonic erythropoietic development is inaccessible for in vivo study, an in vitro model allowing the study of this process at both the cellular and molecular levels is necessary. Human embryonic stem cells (hESCs) provide a potential model of early developmental events of cell fate commitment which includes the study of embryonic hematopoiesis. 28 Recently, hESCs have been shown to respond to a combination of hematopoietic cytokines and BMP-4 that promotes hESC differentiation toward hematopoietic cell fate. 29 However, in vitro manipulation of hESCs to direct or regulate hematopoietic differentiation and blood lineage development have not been explored. Taking advantage of the ability to effectively differentiate hESCs into hematopoietic progenitors that represent primitive erythroid cells by CFU assays, the availability o...

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Hematopoietic Progenitor Cells Derived from Embryonic Stem Cells: Analysis of Gene Expression

Cited by 22 publications

References 40 publications

Morphogenetic plasticity of adult human pancreatic islets of Langerhans

Morphogenetic plasticity of adult human pancreatic islets of Langerhans

Development of primitive and definitive hematopoiesis from nonhuman primate embryonic stem cells in vitro

VEGF-A165 augments erythropoietic development from human embryonic stem cells

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