CD34+CD38- hematopoietic precursors derived from human embryonic stem cells exhibit an embryonic gene expression pattern

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

doi:10.1182/blood-2003-10-3575

Cited by 58 publications

(56 citation statements)

References 45 publications

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“…The resulting expression profiles were virtually identical to those from the first hybridization, but with only 70% of the original intensities. This phenomenon has already been described by other users of this cDNA microarray platform (30). We also presented data only from the first experiment, in agreement with published data.…”

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confidence: 80%

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

et al. 2007

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To extend our knowledge of target proteins in endothelial cells infected with the meningitis-causing pathogen Neisseria meningitidis, we characterized the interaction between the bacterial and human brain microvascular endothelial cell (HBMEC) monolayers. By use of human cDNA microarrays, transcriptional analysis revealed distinct responses to 4 and 8 h of infection. We also addressed the question of whether the major virulence factor of meningococci, i.e., the capsule, influences the host cell response. Of the 1,493 (at 4 h postinfection) and 1,246 (at 8 h postinfection) genes with altered expression upon bacterial contact, about 49.4% and 45%, respectively, depended on capsule expression. In particular, we identified an increase of expression for genes encoding proteins involved in bacterial adhesion and invasion. High levels of apoptosis-related gene (bad, bak, asp, and immediate-early response gene 1) expression could also be detected in infected cells. Further analyses confirmed that HBMECs displayed several hallmarks of apoptosis in response to N. meningitidis infection, namely, phosphatidylserine translocation and activation of caspase 3 and AMP-activated protein kinase ␣. Moreover, several differentially regulated genes not previously known to respond to meningococcal infection were identified. Of these, genes encoding cell adhesion proteins (CD44, CD98, and CD99), genes involved in downstream signaling of integrins (integrin-linked kinase, mitogen-activated protein kinase kinase 1, and mitogen-activated protein kinase kinase kinase 10) as well as negative regulators of these pathways (dualspecificity phosphatases 1, 5, and 14 and G protein pathway suppressor 2), and genes involved in cytoskeleton reorganization (those encoding Arp2/3, p34-arc, actinin alpha 1, vasodilatator-stimulated protein, and Wiskott-Aldrich syndrome protein) were the most prominent. This global transcriptional analysis creates a new platform for further molecular and cellular analysis of the interaction between N. meningitidis and target cells.

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confidence: 80%

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

et al. 2007

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“…Accordingly, it was interesting to investigate the role of Akt phosphorylation in tuberin localization. In the literature, reports can be found describing that ectopic Akt triggers downregulation of tuberin protein amounts (Dan et al, 2002;Liu et al, 2006), whereas others describe tuberin protein levels to remain unaffected by Akt (Manning et al, 2002). Importantly, although Akt activity is known to be induced upon mitogenic stimulation (Wullschleger et al, 2006), tuberin protein amounts are constant (Soucek et al, 1997;Miloloza et al, 2000;Manning et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Akt regulates nuclear/cytoplasmic localization of tuberin

2006

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“…1b). To distinguish the developmental stage of the erythroids, we analyzed hematopoietic colonies for the expression patterns of the β-cluster globin genes 20 . All the erythroid and multilineage colonies expressed mainly the embryonic ε-and fetal γ-globin genes; no β-globin gene message was detected (data not shown), suggesting a primitive yolk sac-like status.…”

Section: Hes-bcs Have Hemangioblast Characteristicsmentioning

confidence: 99%

Generation of functional hemangioblasts from human embryonic stem cells

et al. 2007

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Recent evidence suggests the existence of progenitor cells in adult tissues that are capable of differentiating into vascular structures as well as into all hematopoietic cell lineages. Here we describe an efficient and reproducible method for generating large numbers of these bipotential progenitors-known as hemangioblasts-from human embryonic stem (hES) cells using an in vitro differentiation system. Blast cells expressed gene signatures characteristic of hemangioblasts, and could be expanded, cryopreserved and differentiated into multiple hematopoietic lineages as well as into endothelial cells. When we injected these cells into rats with diabetes or into mice with ischemia-reperfusion injury of the retina, they localized to the site of injury in the damaged vasculature and appeared to participate in repair. Injection of the cells also reduced the mortality rate after myocardial infarction and restored blood flow in hind limb ischemia in mouse models. Our data suggest that hES-derived blast cells (hES-BCs) could be important in vascular repair.Although progenitor cells have recently been discovered that can enter the circulation in response to vascular injury and ischemia [1][2][3][4][5] , defining and isolating these cells has proven problematic. Circulating bone marrow-derived cells have also been shown to be important in normal physiologic maintenance and repair of the body's vasculature 6,7 with approximately 1-3% of endothelial cells at any one time being bone marrow-derived. Furthermore, the entire hematopoietic system has been hypothesized to originate from a transient population of hemangioblasts restricted to embryogenesis 8,9 . But recent evidence suggests that hemangioblasts or more mature endothelial progenitors may also exist in adult tissues and umbilical cord blood [2][3][4]10,11 . More direct proof for their existence was provided when the in vitro equivalent of the hemangioblast was isolated using a mouse embryonic stem cell differentiation system 12,13 . Recently a human hemangioblast cell population derived from hES cells was also identified using a procedure that consisted of serum-free differentiation in a mixture of cytokines followed by expansion in serum-containing © 2007 Nature Publishing Group Correspondence should be addressed to R.L. (rlanza@advancedcell.com). Note: Supplementary information is available on the Nature Methods website. COMPETING INTERESTS STATEMENTThe authors declare competing financial interests: details accompany the full-text HTML version of the paper at www.nature.com/ naturemethods.Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions NIH Public Access RESULTS Generation and characterization of blast cells from hES cellsWe developed a simple and efficient method for generating functional blast cells from hES cells with both hematopoietic and endothelial potential in defined media, using a two-step strategy. First, we generated early-stage embryoid bodies (EBs) from hES cells (WA01 (H1)−GFP + ) cultured...

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CD34+CD38- hematopoietic precursors derived from human embryonic stem cells exhibit an embryonic gene expression pattern

Cited by 58 publications

References 45 publications

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

Akt regulates nuclear/cytoplasmic localization of tuberin

Generation of functional hemangioblasts from human embryonic stem cells

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