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DL4-μbeads induce T cell lineage differentiation from stem cells in a stromal cell-free system.
- Source :
-
Nature communications [Nat Commun] 2021 Aug 18; Vol. 12 (1), pp. 5023. Date of Electronic Publication: 2021 Aug 18. - Publication Year :
- 2021
-
Abstract
- T cells are pivotal effectors of the immune system and can be harnessed as therapeutics for regenerative medicine and cancer immunotherapy. An unmet challenge in the field is the development of a clinically relevant system that is readily scalable to generate large numbers of T-lineage cells from hematopoietic stem/progenitor cells (HSPCs). Here, we report a stromal cell-free, microbead-based approach that supports the efficient in vitro development of both human progenitor T (proT) cells and T-lineage cells from CD34 <superscript>+</superscript> cells sourced from cord blood, GCSF-mobilized peripheral blood, and pluripotent stem cells (PSCs). DL4-μbeads, along with lymphopoietic cytokines, induce an ordered sequence of differentiation from CD34 <superscript>+</superscript> cells to CD34 <superscript>+</superscript> CD7 <superscript>+</superscript> CD5 <superscript>+</superscript> proT cells to CD3 <superscript>+</superscript> αβ T cells. Single-cell RNA sequencing of human PSC-derived proT cells reveals a transcriptional profile similar to the earliest thymocytes found in the embryonic and fetal thymus. Furthermore, the adoptive transfer of CD34 <superscript>+</superscript> CD7 <superscript>+</superscript> proT cells into immunodeficient mice demonstrates efficient thymic engraftment and functional maturation of peripheral T cells. DL4-μbeads provide a simple and robust platform to both study human T cell development and facilitate the development of engineered T cell therapies from renewable sources.<br /> (© 2021. The Author(s).)
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Animals
Antigens, CD34 genetics
Antigens, CD34 immunology
Calcium-Binding Proteins genetics
Cell Lineage
Cell- and Tissue-Based Therapy
Cells, Cultured
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells immunology
Humans
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Pluripotent Stem Cells cytology
Pluripotent Stem Cells immunology
Primary Immunodeficiency Diseases genetics
Primary Immunodeficiency Diseases immunology
Primary Immunodeficiency Diseases physiopathology
T-Lymphocytes immunology
T-Lymphocytes transplantation
Adaptor Proteins, Signal Transducing immunology
Calcium-Binding Proteins immunology
Hematopoietic Stem Cells cytology
Lymphopoiesis
Primary Immunodeficiency Diseases therapy
T-Lymphocytes cytology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 34408144
- Full Text :
- https://doi.org/10.1038/s41467-021-25245-8