Thymopentin enhances the generation of T-cell lineage derived from human embryonic stem cells in vitro

Zhu, Mingxia; Wan, Wenli; Li, Haishen; Wang, Jing; Chen, Guian; Ke, Xiaoyan

doi:10.1016/j.yexcr.2014.12.012

Cited by 13 publications

(7 citation statements)

References 33 publications

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“…Its effect seems to be dose dependent [20]. In in vitro conditions, it enhances T-cell lineage proliferation and differentiation, mimicking thymus peptide environment in vivo [21]. In in vivo conditions, it induces the proliferation of lymphocyte precursors and their differentiation to T lymphocytes.…”

Section: Thymopoietinmentioning

confidence: 99%

The Immunoendocrine Thymus as a Pacemaker of Lifespan

Csaba¹

2016

Acta Microbiologica et Immunologica Hungarica

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The thymus develops from an endocrine area of the foregut, and retains the ancient potencies of this region. However, later it is populated by bone marrow originated lymphatic elements and forms a combined organ, which is a central part of the immune system as well as an influential element of the endocrine orchestra. Thymus produces self-hormones (thymulin, thymosin, thymopentin, and thymus humoral factor), which are participating in the regulation of immune cell transformation and selection, and also synthesizes hormones similar to that of the other endocrine glands such as melatonin, neuropeptides, and insulin, which are transported by the immune cells to the sites of requests (packed transport). Thymic (epithelial and immune) cells also have receptors for hormones which regulate them. This combined organ, which is continuously changing from birth to senescence seems to be a pacemaker of life. This function is basically regulated by the selection of self-responsive thymocytes as their complete destruction helps the development (up to puberty) and their gradual release in case of weakened control (after puberty) causes the erosion of cells and intercellular material, named aging. This means that during aging, self-destructive and non-protective immune activities are manifested under the guidance of the involuting thymus, causing the continuous irritation of cells and organs. Possibly the pineal body is the main regulator of the pacemaker, the neonatal removal of which results in atrophy of thymus and wasting disease and its later corrosion causes the insufficiency of thymus. The co-involution of pineal and thymus could determine the aging and the time of death without external intervention; however, external factors can negatively influence both of them.

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Section: Thymopoietinmentioning

confidence: 99%

The Immunoendocrine Thymus as a Pacemaker of Lifespan

Csaba¹

2016

Acta Microbiologica et Immunologica Hungarica

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“…As Notch signaling was shown to be essential for T lymphopoiesis (Mohtashami et al , ), derivation of T cells from hiPSCs/hESCs was achieved with the help of OP9 stromal cells constantly overexpressing the Notch ligand Delta‐like 1 or 4 (DL1 or DL4, respectively). A combination of different cytokines was shown to faithfully induce T‐cell differentiation using either thymopentin, OP9 co‐culture, or transplantation‐based differentiation protocols starting from in vivo progenitor populations or ESCs (Timmermans et al , ; Kennedy et al , ; Sturgeon et al , ; Uenishi et al , ; Zhu et al , ) (see also Table ). Early protocols for the generation of in vitro B cells used OP9 stromal cells and a combination of Flt3‐L and IL‐7 (Cho et al , ; Zambidis et al , ).…”

Section: Psc‐derived Hematopoiesis and The Instructive Role Of Cytokinesmentioning

confidence: 99%

Lost in translation: pluripotent stem cell‐derived hematopoiesis

et al. 2015

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Pluripotent stem cells (PSCs) such as embryonic stem cells or induced pluripotent stem cells represent a promising cell type to gain novel insights into human biology. Understanding the differentiation process of PSCs in vitro may allow for the identification of cell extrinsic/intrinsic factors, driving the specification process toward all cell types of the three germ layers, which may be similar to the human in vivo scenario. This would not only lay the ground for an improved understanding of human embryonic development but would also contribute toward the generation of novel cell types used in cell replacement therapies. In this line, especially the developmental process of mesodermal cells toward the hematopoietic lineage is of great interest. Therefore, this review highlights recent progress in the field of hematopoietic specification of pluripotent stem cell sources. In addition, we would like to shed light on emerging factors controlling primitive and definitive hematopoietic development and to highlight recent approaches to improve the differentiation potential of PSC sources toward hematopoietic stem/progenitor cells. While the generation of fully defined hematopoietic stem cells from PSCs remains challenging in vitro, we here underline the instructive role of cell extrinsic factors such as cytokines for the generation of PSC-derived mature hematopoietic cells. Thus, we have comprehensively examined the role of cytokines for the derivation of mature hematopoietic cell types such as macrophages, granulocytes, megakaryocytes, erythrocytes, dendritic cells, and cells of the B- and T-cell lineage.

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“…The CD4 and CD8 single-positive cells, regulatory T cells (Treg), and natural killer-like T cells (NKT) are generated after further positive and negative selection (2,3). In comparison, human hematopoietic progenitor cells, possessing CD34, CD7, and CD5 markers, undergo similar developmental stages to become mature T cells (4,5).…”

mentioning

confidence: 99%

Role of WW Domain-containing Oxidoreductase WWOX in Driving T Cell Acute Lymphoblastic Leukemia Maturation

Huang

Wan

Lin

et al. 2016

Journal of Biological Chemistry

131

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Whether tumor suppressor WWOX (WW domain-containing oxidoreductase) stimulates immune cell maturation is largely unknown. Here, we determined that Tyr-33-phosphorylated WWOX physically binds non-phosphorylated ERK and IκBα in immature acute lymphoblastic leukemia MOLT-4 T cells and in the naïve mouse spleen. The IκBα·ERK·WWOX complex was shown to localize, in part, in the mitochondria. WWOX prevents IκBα from proteasomal degradation. Upon stimulating MOLT-4 with ionophore A23187/phorbol myristate acetate, endogenous IκBα and ERK undergo rapid phosphorylation in <5 min, and subsequently WWOX is Tyr-33 and Tyr-287 de-phosphorylated and Ser-14 phosphorylated. Three hours later, IκBα starts to degrade, and ERK returns to basal or non-phosphorylation, and this lasts for the next 12 h. Finally, expression of CD3 and CD8 occurs in MOLT-4 along with reappearance of the IκBα·ERK·WWOX complex near 24 h. Inhibition of ERK phosphorylation by U0126 or IκBα degradation by MG132 prevents MOLT-4 maturation. By time-lapse FRET microscopy, IκBα·ERK·WWOX complex exhibits an increased binding strength by 1–2-fold after exposure to ionophore A23187/phorbol myristate acetate for 15–24 h. Meanwhile, a portion of ERK and WWOX relocates to the nucleus, suggesting their role in the induction of CD3 and CD8 expression in MOLT-4.

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Thymopentin enhances the generation of T-cell lineage derived from human embryonic stem cells in vitro

Cited by 13 publications

References 33 publications

The Immunoendocrine Thymus as a Pacemaker of Lifespan

The Immunoendocrine Thymus as a Pacemaker of Lifespan

Lost in translation: pluripotent stem cell‐derived hematopoiesis

Role of WW Domain-containing Oxidoreductase WWOX in Driving T Cell Acute Lymphoblastic Leukemia Maturation

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