Lymphoid cell development from fetal hematopoietic progenitors and human pluripotent stem cells

Lymphoid cells encompass the adaptive immune system, including T and B cells and Natural killer T cells (NKT), and innate immune cells (ILCs), including Natural Killer (NK) cells. During adult life, these lineages are thought to derive from the differentiation of long-term hematopoietic stem cells (HSCs) residing in the bone marrow. However, during embryogenesis and fetal development, the ontogeny of lymphoid cells is both complex and multifaceted, with a large body of evidence suggesting that lymphoid lineages arise from progenitor cell populations antedating the emergence of HSCs. Recently, the application of single cell RNA-sequencing technologies and pluripotent stem cell-based developmental models has provided new insights into lymphoid ontogeny during embryogenesis. Indeed, PSC differentiation platforms have enabled de novo generation of lymphoid immune cells independently of HSCs, supporting conclusions drawn from the study of hematopoiesis in vivo. Here, we examine lymphoid development from non-HSC progenitor cells and technological advances in the differentiation of human lymphoid cells from pluripotent stem cells for clinical translation.

Automated summary

Lymphoid cells, including T cells, B cells, NKT cells, and ILCs, play important roles in both adaptive and innate immune systems. While it is believed that these cells derive from HSCs in adult bone marrow, their ontogeny during embryogenesis is complex and involves progenitor cells predating the emergence of HSCs. Recent advancements in single cell RNA-sequencing and pluripotent stem cell-based developmental models provide new insights into lymphoid development and offer potential for clinical translation.