Tu117 - Deep Molecular Comparison Between Lymphoid Progenitor Cells Differentiated from CB or mPB CD34+ Hematopoietic Stem Cells Cultivated on Notch Ligand DLL4 Through a Clinically Compatible Culture Procedure

Ex vivo generated Human lymphoid progenitors (CD34^-CD7⁺) have demonstrated their ability to seed patient thymus and to achieve a polyclonal T cell repertoire reconstitution faster and more efficiently than classical CD34⁺ hematopoietic stem and progenitor cell (HSPC) treatment. Currently under investigation in 3 clinical trials, this approach aims to improve significantly patient prognosis after Hematopoietic Stem Cell Transplantation (HSCT). CD34⁺ HSPC used as starting material are isolated from mobilized peripheral blood (mPB) or from Cord Blood (CB) units.

In preclinical studies, both products demonstrated similar T lymphoid potential in vitro and in vivo. However, impact of CD34⁺ HSPC source was obvious in terms of production efficacy. CB-derived cells were indeed associated with significantly higher expansion and CD34^-CD7⁺ cell purity ( >90%).

Here, we describe a comparative analysis between lymphoid progenitors produced from CB or mPB using a complementary single-cell RNA sequencing (scRNAseq) and mass cytometry (CyTOF) approach. This in-depth characterization revealed a diversity of the CD7⁺ subset, as well as the presence of non-lymphoid cell subsets, differentially represented according to the CD34⁺ HSPC source used. Molecules associated with a known or putative role in thymus homing and function were also differentially expressed between CB and mPB-derived CD34^-CD7⁺ lymphoid progenitors. The potential impact of these differences in the clinics will be assessed. Altogether, our study provides interesting insights on lymphoid cells differentiation and highlights the potential impact of CD34⁺ cell source on advanced therapies production.