In vitro T lymphopoiesis

Author(s):  
R.L. Williams ◽  
J.R. Allred ◽  
B.R. Blazar
Keyword(s):  
2019 ◽  
Author(s):  
Rongqun Guo ◽  
Fangxiao Hu ◽  
Qitong Weng ◽  
Cui Lv ◽  
Hongling Wu ◽  
...  

ABSTRACTAchievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells is a central aim in T cell regenerative medicine. To date, preferentially regenerating T lymphopoiesis in vivo from pluripotent stem cells (PSC) remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial to hematopoietic transition and hematopoietic maturation stages induced in vitro from PSC (iR9-PSC) preferentially generated engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T (iT) cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSC, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The iT cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCRαβ repertoire. The regenerative T lymphopoiesis rescued the immune-surveillance ability in immunodeficient mice. Furthermore, gene-edited iR9-PSC produced tumor-specific-T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T lymphopoiesis from the unlimited and editable PSC source.


Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3362-3364 ◽  
Author(s):  
Yuya Kunisaki ◽  
Sadahiko Masuko ◽  
Mayuko Noda ◽  
Ayumi Inayoshi ◽  
Terukazu Sanui ◽  
...  

Abstract Clearance of apoptotic cells by macrophages is considered important for prevention of inflammatory responses leading to tissue damage. The phosphatidylserine receptor (PSR), which specifically binds to phosphatidylserine (PS) exposed on the surface of apoptotic cells, mediates uptake of apoptotic cells in vitro, yet the physiologic relevance of PSR remains unknown. This issue was addressed by generating PSR-deficient (PSR-/-) mice. PSR-/- mice exhibited severe anemia and died during the perinatal period. In the PSR-/- fetal livers, erythroid differentiation was blocked at an early erythroblast stage. In addition, PSR-/- embryos exhibited thymus atrophy owing to a developmental defect of T-lymphoid cells. Clearance of apoptotic cells by macrophages was impaired in both liver and thymus of PSR-/- embryos. However, this did not induce up-regulation of inflammatory cytokines. These results indicate that during embryonic development, PSR-mediated apoptotic cell uptake is required for definitive erythropoiesis and T lymphopoiesis, independently of the prevention of inflammatory responses. (Blood. 2004;103:3362-3364)


2006 ◽  
Vol 917 (1) ◽  
pp. 724-731 ◽  
Author(s):  
J. PLUM ◽  
M. SMEDT ◽  
B. VERHASSELT ◽  
T. KERRE ◽  
D. VANHECKE ◽  
...  

Cell Research ◽  
2019 ◽  
Vol 30 (1) ◽  
pp. 21-33 ◽  
Author(s):  
Rongqun Guo ◽  
Fangxiao Hu ◽  
Qitong Weng ◽  
Cui Lv ◽  
Hongling Wu ◽  
...  

AbstractAchievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells (PSCs) is a central aim in T cell regenerative medicine. To date, preferentially reconstituting T lymphopoiesis in vivo from PSCs remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial-to-hematopoietic transition and hematopoietic maturation stages in a PSC differentiation scheme (iR9-PSC) in vitro induced preferential generation of engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSCs, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The induced T cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCRαβ repertoire. The regenerative T lymphopoiesis restored immune surveillance in immunodeficient mice. Furthermore, gene-edited iR9-PSCs produced tumor-specific T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T cells from the unlimited and editable PSC source.


1996 ◽  
Vol 25 (3) ◽  
pp. 192-200 ◽  
Author(s):  
Michael Rosenzweig ◽  
Douglas F. Marks ◽  
Donna Hempel ◽  
R. Paul Johnson

2005 ◽  
pp. 31-44
Author(s):  
Michael Rosenzweig ◽  
David T Scadden
Keyword(s):  

Blood ◽  
2013 ◽  
Vol 122 (26) ◽  
pp. 4210-4219 ◽  
Author(s):  
Génève Awong ◽  
Jastaranpreet Singh ◽  
Mahmood Mohtashami ◽  
Maria Malm ◽  
Ross N. La Motte-Mohs ◽  
...  

Key Points Intrathymic T-cell regeneration is facilitated by human proT-cells generated in vitro. In vitro–generated human proT-cells home to the thymus, wherein they restore thymic structure.


Author(s):  
P.L. Moore

Previous freeze fracture results on the intact giant, amoeba Chaos carolinensis indicated the presence of a fibrillar arrangement of filaments within the cytoplasm. A complete interpretation of the three dimensional ultrastructure of these structures, and their possible role in amoeboid movement was not possible, since comparable results could not be obtained with conventional fixation of intact amoebae. Progress in interpreting the freeze fracture images of amoebae required a more thorough understanding of the different types of filaments present in amoebae, and of the ways in which they could be organized while remaining functional.The recent development of a calcium sensitive, demembranated, amoeboid model of Chaos carolinensis has made it possible to achieve a better understanding of such functional arrangements of amoeboid filaments. In these models the motility of demembranated cytoplasm can be controlled in vitro, and the chemical conditions necessary for contractility, and cytoplasmic streaming can be investigated. It is clear from these studies that “fibrils” exist in amoeboid models, and that they are capable of contracting along their length under conditions similar to those which cause contraction in vertebrate muscles.


Author(s):  
John J. Wolosewick ◽  
John H. D. Bryan

Early in spermiogenesis the manchette is rapidly assembled in a distal direction from the nuclear-ring-densities. The association of vesicles of smooth endoplasmic reticulum (SER) and the manchette microtubules (MTS) has been reported. In the mouse, osmophilic densities at the distal ends of the manchette are the organizing centers (MTOCS), and are associated with the SER. Rapid MT assembly and the lack of rough ER suggests that there is an existing pool of MT protein. Colcemid potentiates the reaction of vinblastine with tubulin and was used in this investigation to detect this protein.


Author(s):  
E. J. Kollar

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.


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