Loss of Canonical Notch Signaling Affects Multiple Steps in NK Cell Development in Mice.

Within the hematopoietic system, the Notch pathway is critical for promoting thymic T cell development and suppressing the B and myeloid lineage fates; however, its impact on NK lymphopoiesis is less understood. To study the role of Notch during NK cell development in vivo, we investigated different NK cell compartments and function in Rbp-JkVav-Cre mice, in which , the major transcriptional effector of canonical Notch signaling, was specifically deleted in all hematopoietic cells. Peripheral conventional cytotoxic NK cells in -deleted mice were significantly reduced and had an activated phenotype.

Macrophage colony-stimulating factor receptor marks and regulates a fetal myeloid-primed B-cell progenitor in mice.

Although it is well established that unique B-cell lineages develop through distinct regulatory mechanisms during embryonic development, much less is understood about the differences between embryonic and adult B-cell progenitor cells, likely to underpin the genetics and biology of infant and childhood PreB acute lymphoblastic leukemia (PreB-ALL), initiated by distinct leukemia-initiating translocations during embryonic development. Herein, we establish that a distinct subset of the earliest CD19(+) B-cell progenitors emerging in the E13.5 mouse fetal liver express the colony-stimulating factor-1 receptor (CSF1R), previously thought to be expressed, and play a lineage-restricted role in development of myeloid lineages, and macrophages in particular.

Identification of a Human Natural Killer Cell Lineage-Restricted Progenitor in Fetal and Adult Tissues.

Natural killer (NK) cells are cytotoxic lymphocytes and play a vital role in controlling viral infections and cancer. In contrast to B and T lymphopoiesis where cellular and regulatory pathways have been extensively characterized, the cellular stages of early human NK cell commitment remain poorly understood. Here we demonstrate that a Lin(-)CD34(+)CD38(+)CD123(-)CD45RA(+)CD7(+)CD10(+)CD127(-) population represents a NK lineage-restricted progenitor (NKP) in fetal development, umbilical cord blood, and adult tissues.

NK cell development and function--plasticity and redundancy unleashed.

Bone marrow-derived natural killer (NK) cells constitute the major subset of cytotoxic lymphocytes in peripheral blood. They provide innate defense against intracellular infection or malignancy and contribute to immune homeostasis. Large numbers of NK cells are also present in tissues, including the liver and uterus, where they can mediate immunosurveillance but also play important roles in tissue remodeling and vascularization.

Emergence of NK-cell progenitors and functionally competent NK-cell lineage subsets in the early mouse embryo.

The earliest stages of natural killer (NK)-cell development are not well characterized. In this study, we investigated in different fetal hematopoietic tissues how NK-cell progenitors and their mature NK-cell progeny emerge and expand during fetal development. Here we demonstrate, for the first time, that the counterpart of adult BM Lin(-)CD122(+)NK1.

Identification of an NK/T cell-restricted progenitor in adult bone marrow contributing to bone marrow- and thymic-dependent NK cells.

Although bone marrow (BM) is the main site of natural killer (NK)-cell development in adult mice, recent studies have identified a distinct thymic-dependent NK pathway, implicating a possible close link between NK- and T-cell development in adult hematopoiesis. To investigate whether a potential NK-/T-lineage restriction of multipotent progenitors might take place already in the BM, we tested the full lineage potentials of NK-cell progenitors in adult BM. Notably, although Lin(-)CD122(+)NK1.

From the bone marrow to the thymus: the road map of early stages of T-cell development.

The thymus produces new T cells throughout life but has no self-renewing ability and requires replenishment and recruitment of progenitors derived from the bone marrow. Despite the progress in delineation of mature blood cell development several questions remain regarding T lymphopoiesis. Understanding the developmental stages from multipotent hematopoietic stem cells (HSCs) to the T-cell lineage-restricted progenitors has many potential clinical implications as it is important for understanding malignant transformation in T-cell cancer, accelerating T-cell regeneration after bone marrow transplantation and chemotherapy, and establishing new therapies to treat T-cell immune deficiencies.