Lnk controls mouse hematopoietic stem cell self-renewal and quiescence through direct interactions with JAK2
J. Clin. Invest. Alexey Bersenev, et al. 118:2832 doi:10.1172/JCI35808 [
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Figure 1Mpl–/–Lnk–/– HSCs show decreased self-renewal ability.
(
A) We quantified HSC frequencies of WT,
Mpl–/–,
Lnk–/–, and
Mpl–/–Lnk–/– mice using limiting dilution cBMT. Results are pooled from 3–5 independent experiments. (
B) Top: BM cells from WT,
Mpl–/–,
Lnk–/–, and
Mpl–/–Lnk–/– mice were mixed at 1:1 ratio with CD45.1 competitor cells and transplanted into irradiated recipient mice. Chimerisms of transplanted mice were measured 1, 4, and 8 months after transplant (mean ± SD).
n = 10. Middle panel: Transplant results from WT,
Mpl–/–, and
Mpl–/–Lnk–/– mice when mixed at 9:1 ratio with the competitors. Bottom: Transplant results from
Lnk–/– BM cells when mixed at different ratios with the competitors.
n = 5. *
P < 0.005, WT compared with
Mpl–/–Lnk–/– at the same time points, 2-tailed unequal variance
t test;
#P < 0.005, compared with same strain at 4 months, 2-tailed paired
t test; **
P < 0.05, compared with same strain at 4 months, 2-tailed paired
t test. (
C and
D) Primary transplanted mice were sacrificed at 8 months and total BM cells were transplanted into secondary recipients. (
C) Transplant results from WT,
Mpl–/–, and
Mpl–/–Lnk–/– mice when mixed at 9:1 ratio and
Lnk–/– mice when mixed at 1:19 ratio with the competitors. (
D) Transplant results from WT,
Mpl–/–, and
Mpl–/–Lnk–/– mice when mixed at 3:1 ratio and
Lnk–/– mice when mixed at 1:99 ratio with the competitors. Chimerisms of the primary transplanted mice (mean ± SD) are shown in the left panels and those of the secondary transplant (mean ± SEM) are shown in the right panels. **
P < 0.05;
†P = not significant,
n = 5.
