Single cell transcriptomic of ex vivo-generated lymphoid progenitors from mobilised peripheral blood- or corb blood-derived hematopoietic stem and progenitors cells

We previously established a feeder-free cell therapy platform for the ex vivo generation of lymphoid-primed progenitors using immobilized Delta-like ligand 4 (DLL4), and hereafter known as ProTcell. We demonstrated these progenitors can be generated from hematopoietic stem and progenitors cells originating from cord blood (CB) and mobilized peripheral blood (mPB). In vivo studies demonstrated that adoptive transfer of these progenitors accelerates T cell reconstitution following thymic engraftment (Moirangthem RD et al., 2021 ; Simons L et al., 2018 ; Reimann et al., 2012). To further explore the full therapeutic potential of this cell product, we performed a comprehensive characterization using single-cell RNA sequencing. We confirmed ProTcell samples derived from CB and mPB were highly similar,as they clustered together. Our analysis also revealed the presence of distinct cell subsets within the cellular product characterized mainly by their commitment to lymphoid lineages. We highlighted strong similarities with early stages of T cell development, underscoring the physiological relevance of our system.