Meis1 regulates self-renewal of HSCs in a cell autonomous manner.

<p>(A) Experimental strategy for analyzing the function of Meis1 in HSCs. Mice with chimeric BM were generated by transplanting CD34⁻ LSK cells (50 cells/mouse) from <i>Mx1-Cre</i>⁺<i>Meis1</i>^fl/fl or control <i>Meis1</i>^fl/fl mice (CD45.2) and an equal number of CD34⁻ LSK cells from wild-type mice (CD45.1/CD45.2) with CD45.1 BM supports cells in lethally irradiated CD45.1 recipient mice. A subset of mice was treated with poly(I:C) three months after transplantation. (B) Mean percentages of CD45.2⁺ cells ± SD in the peripheral blood derived from <i>Meis1</i>^fl/fl (n = 6; open circles) and <i>Mx1-Cre⁺ Meis1</i>^fl/fl (n = 6; closed circles) CD34⁻ LSK cells after poly(I:C) treatment. Initial engraftment of CD45.2⁺ was normalized to 100% for each mouse. *p<0.05 and **p<0.01. (C) Histogram represents mean (± SD) contribution of the indicated splenic cell populations derived from <i>Meis1</i>^fl/fl (n = 6; open bars) and <i>Mx1-Cre</i>⁺<i>Meis1</i>^fl/fl (n = 6; solid bars) CD34⁻ LSK cells three months after poly(I:C) treatment. *p<0.05 and **p<0.01. (D) Mean percentages of CD45.2⁺ cells ± SD in the peripheral blood derived from <i>Meis1</i>^fl/fl (n = 6; open circles) or <i>Mx1-Cre⁺ Meis1</i>^fl/fl (n = 6; closed circles) CD34⁻ LSK cells after secondary transplantation. *p<0.05 and **p<0.01. (E) Total numbers (left) and proportions (right) of different colony types produced by CD34⁻ LSK cells from poly(I:C)-treated <i>Mx1-Cre⁺ Meis1</i>^fl/fl and control <i>Meis1</i>^fl/fl mice (n = 3 per each group). Cultures were assessed on day 14 for granulocyte (CFU-G), monocytes (CFU-M), granulocyte-monocyte (CFU-GM), erythroid (BFU-E) and mixed (CFU-GEMM) colony formation. The data are the means of three-independent experiments. (F) Representative photographs of 14 day colonies derived from CD34⁻ LSK cells from poly(I:C)-treated <i>Mx1-Cre⁺ Meis1</i>^fl/fl- and control <i>Meis1</i>^fl/fl mice (×40 magnification).