Identification of a novel, human multilymphoid progenitor in cord blood

Hao, Qian-Lin; Zhu, Judy; Price, Mitchell R.; Payne, Kimberly J.; Barsky, Lora; Crooks, Gay M.

doi:10.1182/blood.v97.12.3683

Cited by 185 publications

(185 citation statements)

References 40 publications

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“…Such cells were found in fetal BM and in cord blood (27). More recently, these populations were studied in the thymus: it was found that CD34 ϩ CD7 Ϫ cells are multipotent, CD34 ϩ CD7 int cells are lymphoid precursors including B cell precursor activity and the CD34 ϩ CD7 high population consists of T/NK precursors (21).…”

Section: Discussionmentioning

confidence: 99%

Generation of T Cells from Human Embryonic Stem Cell-Derived Hematopoietic Zones

Timmermans

Velghe

Vanwalleghem

et al. 2009

The Journal of Immunology

181

151

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Human embryonic stem cells (hESC) are pluripotent stem cells. A major challenge in the field of hESC is the establishment of specific differentiation protocols that drives hESC down a particular lineage fate. So far, attempts to generate T cells from hESC in vitro were unsuccessful. In this study, we show that T cells can be generated in vitro from hESC-derived hematopoietic precursor cells present in hematopoietic zones (HZs). These zones are morphologically similar to blood islands during embryonic development, and are formed when hESC are cultured on OP9 stromal cells.

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Section: Discussionmentioning

confidence: 99%

Generation of T Cells from Human Embryonic Stem Cell-Derived Hematopoietic Zones

Timmermans

Velghe

Vanwalleghem

et al. 2009

The Journal of Immunology

181

151

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“…The former diseases are known to be rich in cytokines in the lesional tissues as compared to the latter diseases. 8,19,21,22 In the reactive lymphoid hyperplasia, cytokines are also abundantly produced. 19 These findings indicated the connection of the number of ABCG2-high plasma cells with cytokine contents in the lesional tissues.…”

Section: Discussionmentioning

confidence: 99%

“…5,[7][8][9] To our knowledge, results of immunohistochemical detection of the expression of ABCG2 in lymphoid tissues have not been reported. The present study showed the strong signals for ABCG2 in a small population of CD138-positive cells with ample cytoplasm and condensed chromatin structures in the nucleus.…”

Section: Discussionmentioning

confidence: 99%

“…5,7 The CD34-negative, CD7-positive, and lineage-negative population containing lymphoid progenitor cells also express ABCG2. 8,9 In addition to the transport of a broad range of xenobiotics, ABCG2 is involved in protection of cells from endogenous and exogenous stress factors, including proinflammatory mediators and hypoxia. 10 Recently, Evseenko et al 11 reported that reduced expression of ABCG2 resulted in idiopathic human fetal growth restriction, thus suggested that ABCG2 is a placental survival factor.…”

mentioning

confidence: 99%

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Synergistic effect of interleukin-6 and endoplasmic reticulum stress inducers on the high level of ABCG2 expression in plasma cells

Nakamichi

Morii

Ikeda

et al. 2009

Laboratory Investigation

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ABCG2 is a transporter preferentially expressed in a primitive subpopulation of cells and recently reported as a surviving factor for trophoblasts. To date, manner of ABCG2 expression in lymphoid tissues is not known. Immunohistochemically, strong ABCG2 expression was found in a small proportion of plasma cells mainly located in the interfollicular space of lymphoid tissues. The number of ABCG2-high plasma cells increased in interleukin-6-(IL-6) rich lesions, such as Castleman's disease of plasma cell type. Plasma cells are subjected to endoplasmic reticulum (ER) stress when excess proteins are synthesized, and IL-6 stimulates protein synthesis. Therefore, the effect of IL-6 and ER stress on ABCG2 expression in plasma cells was examined. The expression level of ABCG2 increased by treatment with either IL-6 or ER stress inducers, and further increased with both. The promoter analysis revealed that the effect of IL-6 and ER stress inducers was mediated through the site overlapping XBP-1 and HIF-1 binding sequences. Knocked-down of ABCG2 by siRNA or ABCG2 inhibitor reduced plasma cell viability under ER stress. These suggest that ABCG2 is a surviving factor for plasma cells. To our knowledge, this is the first study reporting the effect of ER stress on ABCG2 expression.

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“…[32]. In order to demonstrate the functionality of the differentiated cells, the cytolytic activity of this cell population was also evaluated, and proved to be similar to freshly isolated NK cells from cord blood and bone marrow [33], as well as NK cells derived from a CD34 + CD7 + population [30]. Although the culture conditions were not ideal to generate T cells, by day 12, 8.75±0.48% of the cells in culture expressed CD3, a marker of T cells.…”

Section: Discussionmentioning

confidence: 99%

Generation of functional natural killer and dendritic cells in a human stromal-based serum-free culture system designed for cord blood expansion

Frias

Porada

Crapnell

et al. 2008

Experimental Hematology

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Objective-We have previously reported the ability of a mesenchymal stem cell (MSC)-based serum-free culture system to expand human cord blood (CB) hematopoietic stem cells (HSC) along the myeloid pathway and simultaneously generate a CD7 + CD34 -population. In this study, we investigated the ability of the CD7 + CD34 -population to differentiate into natural killer and dendritic cells.Materials and Methods-CB CD34 + cells were expanded over a MSC layer in serum-free medium supplemented with SCF, bFGF, LIF, and FL for 2 weeks. Cultured cells were harvested and CD7 + CD34 -Lin -cells sorted and plated for two additional weeks in either natural killer (NK)-or dendritic cell (DC)-inductive medium.Results-culture of CD34 + cells for the first 2 weeks in this system resulted in expansion of the stem cell pool and the myeloid component of the graft, and also produced a 58 fold-increase in the CD7 + CD34 -cell population. When sorted CD7 + CD34 -Lin -cells were induced towards a NK phenotype, further expansion was observed during this time in culture, and differentiation was confirmed by cytotoxic activity and by flow cytometry, with cells displaying CD16 and CD56 in the absence of CD3. The generation of DC cells in culture was also verified by observing both the characteristic dendritic morphology and the dendritic phenotypes HLA-DR bright CD123 bright CD11c -and HLA-DR bright CD11c + .Conclusion-These results demonstrate the ability of an ex-vivo culture system to drive the expansion of human CB HSCs while promoting the immune maturation of the graft and the generation of DC and NK cells that could then be utilized for adoptive cancer cellular immunotherapy.

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Identification of a novel, human multilymphoid progenitor in cord blood

Cited by 185 publications

References 40 publications

Generation of T Cells from Human Embryonic Stem Cell-Derived Hematopoietic Zones

Generation of T Cells from Human Embryonic Stem Cell-Derived Hematopoietic Zones

Synergistic effect of interleukin-6 and endoplasmic reticulum stress inducers on the high level of ABCG2 expression in plasma cells

Generation of functional natural killer and dendritic cells in a human stromal-based serum-free culture system designed for cord blood expansion

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