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DL4-μbeads induce T cell lineage differentiation from stem cells in a stromal cell-free system.

Authors :
Trotman-Grant AC
Mohtashami M
De Sousa Casal J
Martinez EC
Lee D
Teichman S
Brauer PM
Han J
Anderson MK
Zúñiga-Pflücker JC
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).)

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