Investigating increased hematopoietic stem cell fitness in a novel mouse model

Figures & data

Figure 1. Overexpression of RasGRP1 bestows an advantage to stem cells in the context of native BM but not in BMT. Injection of our novel RoLoRiG mouse model with a single dose of polyinosinicpolycytidylic acid (pIpC) leads to Mx1CRE-mediated excision of the stop codon flanked by LoxP sites and expression of a RasGRP1-ires-GFP cassette. A single pIpC injection results in RasGRP1 overexpression in a portion of the haematopoietic cells in the BM in conjunction with GFP. Under conditions of native Hematopoiesis, RasGRP1-overexpressing stem cell display an increased fitness phenotype and, over time, GFP-positive cells fill the entire BM compartment. In native Hematopoiesis, an increase in most stem cell populations is evident in RoLoRiG-derived BM. By stark contrast, when a bone marrow transplantation (BMT) approach is used, RoLoRiG-derived stem cells (LSK cells) do not have any obvious advantage over wild type-derived LSK cells, and only mild effects are detected in the BM cell population.PI3K signals play important roles in Hematopoiesis (50, 51) and aberrantly elevated PI. Figure was generated using Biorender.com