Distinct roles of IL-7 and stem cell factor in the OP9-DL1 T-cell differentiation culture system

Wang, Hongfang; Pierce, Lauren; Spangrude, Gerald J.

doi:10.1016/j.exphem.2006.08.001

Cited by 47 publications

(42 citation statements)

References 64 publications

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“…These data indicate that, in the YS, morphologically undifferentiated features were observed in the cell populations with hematopoietic activity. (Wang et al 2006). As shown in Fig.…”

Section: Morphology Of Ys Cells In Each Population At E105 and E125mentioning

confidence: 80%

Identification of a yolk sac cell population with hematopoietic activity in view of CD45/c-Kit expression

Yamasaki

Nobuhisa

Ramadan

et al. 2011

Development, Growth &Amp; Differentiation

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During murine embryonic development, primitive hematopoiesis occurs in the yolk sac (YS). Recent studies have shown that the YS also harbors definitive hematopoietic activity. However, the population of YS cells contributing to definitive hematopoiesis has not been identified. In this study, we characterized the hematopoietic cell populations in the YS of mouse embryos from E9.5 to E14.5 in view of the expression profiles of CD45 and c-Kit. The YS cells from E9.5 to E11.5 could be divided into six populations:high c-Kit high and CD45 high c-Kit very low . Among these populations, CD45 low c-Kit high cells showed the highest multilineage hematopoietic colony-forming activity. Later in development, the YS cells from E12.5 to E14.5 lost the second and fourth populations (i.e., they retained CD45 ) c-Kithigh c-Kit high and CD45 high c-Kit very low cells), and concurrently with the disappearance of the CD45 low cKit high population, no significant hematopoietic activity was found in any of the populations on and after E12.5. CD45 low c-Kit high YS cells, which had a round morphology with a large nucleus, possessed the ability to differentiate into myeloid and B lymphoid cells when cultured with stromal cells. These findings suggest that CD45 low cKit high YS cells include more undifferentiated cells than the other YS cell populations and possess in vitro potency to differentiate into multilineage hematopoietic cells. Furthermore, this cell population disappears from the YS at around E12.5, when the site of hematopoiesis has already shifted to the fetal liver and the placenta.

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“…These data indicate that, in the YS, morphologically undifferentiated features were observed in the cell populations with hematopoietic activity. (Wang et al 2006). As shown in Fig.…”

Section: Morphology Of Ys Cells In Each Population At E105 and E125mentioning

confidence: 80%

Identification of a yolk sac cell population with hematopoietic activity in view of CD45/c-Kit expression

Yamasaki

Nobuhisa

Ramadan

et al. 2011

Development, Growth &Amp; Differentiation

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“…Complementary studies from other models show both ID gene expression and SCF signaling promote NK-cell development and expansion while inhibiting T-and B-cell development. [21][22][23][24] Therefore, these findings have important implications for in vitro studies of lymphoid development from hESCs. For personal use only.…”

mentioning

confidence: 99%

Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood–derived hematopoietic progenitor cells

Martin

Woll

et al. 2008

Blood

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Hematopoietic progenitor cells derived from human embryonic stem cells (hESCs) develop into diverse mature hematopoietic lineages, including lymphocytes. Whereas functional natural killer (NK) cells can be efficiently generated in vitro from hESC-derived CD34 ؉ cells, studies of T-and B-cell development from hESCs have been much more limited. Here, we demonstrate that despite expressing functional Notch-1, CD34 ؉ cells from hESCs did not derive T cells when cocultured with OP9 cells expressing Delta-like 1, or in fetal thymus organ culture. hESC-derived CD34 ؉ cells also did not produce B cells in vitro. In contrast, CD34 ؉ cells isolated from UCB routinely generated T and B cells when cultured in the same conditions. Notably, both undifferentiated hESCs, and sorted hESC-derived populations with hematopoietic developmental potential exhibited constitutive expression of ID family genes and of transcriptional targets of stem cell factor-induced signaling. These pathways both inhibit T-cell development and promote NK-cell development. Together, these results demonstrate fundamental differences between hESC-derived hematopoietic progenitors and analogous primary human cells. Therefore, hESCs can be more readily supported to differentiate into certain cell types than others, find- IntroductionHuman embryonic stem cells (hESCs) provide an important model system to define the mechanisms that mediate cellular development. hESC-derived hematopoietic progenitor cells efficiently produce erythroid, myeloid, and lymphoid lineage cells in vitro. [1][2][3][4] We previously defined an in vitro culture system to generate natural killer (NK) cells from hESCs. 5 hESC-derived NK cells express surface receptors characteristic of primary NK cells, kill tumor target cells, and produce interferon-␥ when stimulated with cytokines. These results suggest that hESC-derived progenitors may also readily commit to the T-cell lineage in vitro, since T and NK lymphocytes are developmentally closely related. 6,7 One study has used an in vivo model to examine the T-cell potential of hESCs. 8 Galic et al injected hESC-derived hematopoietic progenitor cells into human thymus/fetal liver (Thy/Liv) grafts in severe combined immunodeficient-human (SCID-hu) mice. This study demonstrated T-cell development after 3 to 5 weeks in vivo, although in a less efficient manner than what has been observed with hematopoietic progenitor cells from human fetal liver (FL), bone marrow (BM), or umbilical cord blood (UCB) 9-11 evaluated in SCID-hu mice. Although useful, SCID-hu mice are not optimal to evaluate development of specific phenotypic cell populations over time, and the effects of specific molecular signaling pathways are difficult to quantify via this SCID-hu system. Therefore, in vitro models of lymphocyte development are needed, although despite the considerable interest in hematopoietic development of hESCs, in vitro studies have not provided significant evidence of functional T and B lymphocyte maturation of hESC-derived hematopoietic progenitors. Al...

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“…If instead they were cocultured on OP9-DL1 with rSCF, IL-7, and Flt3L for 9 days, then CD4 + , CD4 + CD8 + , and CD8 + T lymphocytes were produced (Fig. 3E-c) [23,24]. These results indicate that HAR-ND cells have the potential to produce mature blood cell types under the right culture conditions.…”

Section: Cd48mentioning

confidence: 63%

Nonmarrow Hematopoiesis Occurs in a Hyaluronic-Acid-Rich Node and Duct System in Mice

Hwang

Lee

Park

et al. 2014

Stem Cells and Development

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Distinct roles of IL-7 and stem cell factor in the OP9-DL1 T-cell differentiation culture system

Cited by 47 publications

References 64 publications

Identification of a yolk sac cell population with hematopoietic activity in view of CD45/c-Kit expression

Identification of a yolk sac cell population with hematopoietic activity in view of CD45/c-Kit expression

Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood–derived hematopoietic progenitor cells

Nonmarrow Hematopoiesis Occurs in a Hyaluronic-Acid-Rich Node and Duct System in Mice

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