JAK2V617F induces a loss of self-renewal activity and HSC numbers and leads to a lineage bias when limited HSCs are transplanted.

<p>(A) Relative chimerism following transplantation of 10⁶ or 10⁵ JAK2^V617F or wild type (WT) whole bone marrow (BM) 6–10 months post-pIpC along with 5×10⁵ whole BM competitor cells into eight recipient mice. Average chimerism was lower in mice receiving JAK2^V617F cells (<i>p</i> = 0.03). (B) The relative myeloid (purple) versus lymphoid (green) contribution in each of the recipient animals were determined by calculating a ratio between the contribution to the myeloid compartment [Donor GM/(Donor GM+Competitor GM)] and lymphoid compartment [Donor BT/(Donor BT+Competitor BT)]. (C) Relative chimerism in primary peripheral blood (PB) (white bars) in the eight animals receiving 10⁵ cells compared to levels of PB chimerism in the 16 secondary recipients (two per primary animal, grey bars) in two independent transplantation experiments. An “X” represents a recipient that showed less than 1% chimerism at 24 wk posttransplantation, and a ∧ represents a recipient that only had contribution to the lymphoid lineages. (D) The relative myeloid (purple) versus lymphoid (green) contribution in each of the secondary recipient animals were determined by calculating a ratio between the contribution to the myeloid and lymphoid compartments as in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001576#pbio-1001576-g001" target="_blank">Figure 1B</a>. (E) The FACS isolation strategy for CD45⁺/EPCR⁺/CD48⁻/CD150⁺ (E-SLAM) cells. The panels are gated on viable white blood cells and show E-SLAM gates for WT (top) and JAK2^V617F (bottom). (F) The frequency of E-SLAM HSCs per 10⁵ viable bone marrow (BM) cells in four WT and four JAK2^V617F mice 6–10 mo following pIpC injection from four independent experiments. The frequency is reduced in JAK2^V617F animals (<i>p</i> = 0.0288).