| abstract |
Disclosed herein are compositions and methods for a cell culture system for differentiating stem cells into, e.g., engraftable hematopoietic progenitor cells (HPCs), myeloid and/or lymphoid hematopoietic cells. In particular, the invention relates to producing hemogenic clusters of cells from pluripotent stem cells (e.g., embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs)), culturing the clusters of cells to form a vascular organoid, and derivation of HPCs, natural killer (NK) cells, or myeloid cells using the vascular organoid. The present disclosure further relates to methods of modifying various stem cells and/or hematopoietic cells to, e.g., suppress the proliferation of tumor cells, eliminate senescent cells, modulate pathogen infection (e.g., bacterial infection or viral infection) or inhibit pathogen infection, and uses thereof. In certain aspects, stem cells and/or NK cells provided herein lack expression of NKG2A and/or function, or show reduced expression and/or function of NKG2A. In certain other aspects, stem cells and/or NK cells provided herein comprise modified NKG2A. Methods of using cells of the present disclosure, e.g., in the treatment of cancer and infectious disease are also provided. |