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. 2008 Dec 12;113(13):2924–2933. doi: 10.1182/blood-2008-02-138008

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© 2009 by The American Society of Hematology

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Systemic induction of SHIP deficiency compromises the capacity of HSCs to mediate long-term multilineage repopulation. (A) Flow cytometric quantitation of KLSCD48 HSCs in the BM of MxCreSHIP^flox/flox (CD45.2) mice and SHIP^flox/flox (CD45.2) controls 21 days after poly I:C treatment (n ≥ 3). (B) Percentage of global repopulation in PB at the indicated times after transplantation by WBM cells from SHIP-ablated MxCreSHIP^flox/flox (CD45.2) donors and WT-Ly5.1 (CD45.1) control donors (n ≥ 9). (C) RU activity from SHIP-ablated MxCreSHIP^flox/flox (CD45.2) donors and WT-Ly5.1 (CD45.1) control donors (n ≥ 9). (D) Representative dual-color contour plots that illustrate the level of PB reconstitution at 24 weeks after transplantation from SHIP-ablated MxCreSHIP^flox/flox (CD45.2) BM donors and WT-Ly5.1 (CD45.1) BM competitor donors. (E) Percentage PB repopulation for the indicated lymphoid or myeloid lineage by WBM cells in a competitive transplantation of SHIP-ablated MxCreSHIP^flox/flox (CD45.2) and WT-Ly5.1 (CD45.1) BM competitor cells (n ≥ 9). Before death, the level of donor reconstitution was assessed in PB. (F) Percentage BM repopulation for the indicated myeloid (Mac1), granulocytic (Gr1), megakaryocytic (CD41), or erythroid (Ter119) lineage by WBM cells in a competitive transplantation of SHIP-ablated MxCreSHIP^flox/flox (CD45.2) and WT-Ly5.1 (CD45.1) BM competitor cells (n ≥ 9). At death, the level of donor reconstitution was assessed in BM. Significance was established using the unpaired Student t test (*P < .05; **P < .005; ***P < .001). Errors shown represent the SEM; ■, cells derived from MxCreSHIP^flox/flox BM; , cells derived from SHIP^flox/flox (A) or WT-Ly5.1 BM (B,C,E,F).

Inline graphic — Systemic induction of SHIP deficiency compromises the capacity of HSCs to mediate long-term multilineage repopulation. (A) Flow cytometric quantitation of KLSCD48 HSCs in the BM of MxCreSHIP^flox/flox (CD45.2) mice and SHIP^flox/flox (CD45.2) controls 21 days after poly I:C treatment (n ≥ 3). (B) Percentage of global repopulation in PB at the indicated times after transplantation by WBM cells from SHIP-ablated MxCreSHIP^flox/flox (CD45.2) donors and WT-Ly5.1 (CD45.1) control donors (n ≥ 9). (C) RU activity from SHIP-ablated MxCreSHIP^flox/flox (CD45.2) donors and WT-Ly5.1 (CD45.1) control donors (n ≥ 9). (D) Representative dual-color contour plots that illustrate the level of PB reconstitution at 24 weeks after transplantation from SHIP-ablated MxCreSHIP^flox/flox (CD45.2) BM donors and WT-Ly5.1 (CD45.1) BM competitor donors. (E) Percentage PB repopulation for the indicated lymphoid or myeloid lineage by WBM cells in a competitive transplantation of SHIP-ablated MxCreSHIP^flox/flox (CD45.2) and WT-Ly5.1 (CD45.1) BM competitor cells (n ≥ 9). Before death, the level of donor reconstitution was assessed in PB. (F) Percentage BM repopulation for the indicated myeloid (Mac1), granulocytic (Gr1), megakaryocytic (CD41), or erythroid (Ter119) lineage by WBM cells in a competitive transplantation of SHIP-ablated MxCreSHIP^flox/flox (CD45.2) and WT-Ly5.1 (CD45.1) BM competitor cells (n ≥ 9). At death, the level of donor reconstitution was assessed in BM. Significance was established using the unpaired Student t test (*P < .05; **P < .005; ***P < .001). Errors shown represent the SEM; ■, cells derived from MxCreSHIP^flox/flox BM; , cells derived from SHIP^flox/flox (A) or WT-Ly5.1 BM (B,C,E,F).