Modeling Human Fetal Hematopoiesis in Humanized Mice

Due to difficulties to access primary human bone marrow samples and age or donor effects, human hematopoiesis has long remained far less well characterized than in the mouse. Despite recent progresses in single-cell RNA profiling only little is known as to phenotype, function and developmental trajectories of human lymphomyeloid progenitors and precursors. This is especially true regarding the developmental architecture of the lymphoid lineage which has been the subject of persistent controversies over the past decades. Here, we describe an original approach of in vivo modeling of human fetal hematopoiesis immunodeficient NSG mice engrafted with neonatal CD34⁺ hematopoietic progenitor cells (HPCs) allowing for rapid identification and isolation of lymphomyeloid developmental intermediates.