The expansion of thymopoiesis in neonatal mice is dependent on expression of high mobility group a 2 protein (Hmga2).

Cell number in the mouse thymus increases steadily during the first two weeks after birth. It then plateaus and begins to decline by seven weeks after birth. The factors governing these dramatic changes in cell production are not well understood. The data herein correlate levels of High mobility group A 2 protein (Hmga2) expression with these temporal changes in thymopoiesis. Hmga2 is expressed at high levels in murine fetal and neonatal early T cell progenitors (ETP), which are the most immature intrathymic precursors, and becomes almost undetectable in these progenitors after 5 weeks of age. Hmga2 expression is critical for the initial, exponential expansion of thymopoiesis, as Hmga2 deficient mice have a deficit of ETPs within days after birth, and total thymocyte number is repressed compared to wild type littermates. Finally, our data raise the possibility that similar events occur in humans, because Hmga2 expression is high in human fetal thymic progenitors and falls in these cells during early infancy

Use of Busulfan to Condition Mice for Bone Marrow Transplantation.

Myeloablative gamma irradiation has traditionally been used to condition mice prior to bone marrow transplantation. However, irradiation induces high levels of inflammation that may alter patterns of reconstitution. In addition, gamma irradiators are being removed from many facilities for security reasons. Alternative conditioning regimens are thus needed. Here, we describe a protocol for the use of busulfan to condition mice for bone marrow transplantation and several of the variables to consider for effective implementation. For complete details on the use and execution of this protocol, please refer to Montecino-Rodriguez et al. (2019)

Murine B-1 B Cell Progenitors Initiate B-Acute Lymphoblastic Leukemia with Features of High-Risk Disease

B-1 and B-2 B cells derive from distinct progenitors that emerge in overlapping waves of development. The number of murine B-1 progenitors peaks during fetal development whereas B-2 B cell production predominates in adult bone marrow. Many genetic mutations that underlie B-acute lymphoblastic leukemia (B-ALL) occur in the fetus, at which time B-1 progenitor numbers are high. However, whether B-ALL can initiate in B-1 progenitors is unknown. In the present study, we report that BCR-ABL-transformed murine B-1 progenitors can be B-ALL cells of origin and demonstrate that they initiate disease more rapidly than do oncogene-expressing B-2 progenitors. We further demonstrate that B-1 progenitors exhibit relative resistance to apoptosis and undergo significant growth following oncogene expression, and we propose that these properties underlie the accelerated kinetics with which they initiate leukemia. These results provide a developmental perspective on the origin of B-ALL and indicate B cell lineage as a factor influencing disease progression