Figure 3
Figure 3. The influence of JAK2V617F and TET2KD on hematopoietic stem/progenitor cells. The proportion (A,C) and absolute numbers of LSKs and LKs (B,D), and the absolute numbers of nucleated cells in the femur (1 per mouse; upper column), spleen (middle column), and body (bottom column) of recipients transplanted with 4 types of cells at 20 to 28 weeks (n = 5-9) (A-B) and at 6 to 8 weeks (n = 4) (C-D) after transplantation. Cell numbers in the body were calculated by summing estimated numbers in whole-body BM and in the spleen, as previously described.34,35 (A) Compared with WT mice, TET2KD mice and double-mutant mice showed increased BM-LSK frequencies, and JAK2V617F mice showed decreased spleen-LSK frequencies; JAK2V617F and double-mutant mice showed increased BM-LK frequencies and spleen-LK frequencies. (B) Compared with WT mice, JAK2V617F mice showed decreased nucleated cells in the femur, spleen, and body. Consequently, LSKs and LKs decreased in the femur, spleen, and body of recipients of JAK2V617F cells. Compared with JAK2V617F mice, double-mutant mice showed increased nucleated cells, LSKs, and LKs in the femur, spleen, and body, and double-mutant mice had comparable numbers of LSKs and LKs in the body as WT mice. (C) Compared with WT mice, TET2KD mice showed increased BM- and spleen-LSK frequencies, and JAK2V617F mice and double-mutant mice showed decreased spleen-LSK frequencies; TET2KD mice and double-mutant mice showed increased BM- and spleen-LK frequencies, and JAK2V617F mice showed increased spleen-LK frequencies. (D) Compared with WT mice, TET2KD mice showed increased nucleated cells in the spleen and body, and increased LSKs and LKs in the femur, spleen, and body; JAK2V617F mice showed increased LSKs and LKs in the spleen; double-mutant mice showed increased LSKs in the body and increased LKs in the femur, spleen, and body. Error bars represent standard deviation. *P < .05 and **P < .01 vs WT mice; †P < .05 and ††P < .01 vs JAK2V617F mice. In the bottom column, the gray bar represents the average cell number in whole BM, the black bar represents that in spleen, and the sum of both represents that in body.

The influence of JAK2V617F and TET2KD on hematopoietic stem/progenitor cells. The proportion (A,C) and absolute numbers of LSKs and LKs (B,D), and the absolute numbers of nucleated cells in the femur (1 per mouse; upper column), spleen (middle column), and body (bottom column) of recipients transplanted with 4 types of cells at 20 to 28 weeks (n = 5-9) (A-B) and at 6 to 8 weeks (n = 4) (C-D) after transplantation. Cell numbers in the body were calculated by summing estimated numbers in whole-body BM and in the spleen, as previously described.34,35  (A) Compared with WT mice, TET2KD mice and double-mutant mice showed increased BM-LSK frequencies, and JAK2V617F mice showed decreased spleen-LSK frequencies; JAK2V617F and double-mutant mice showed increased BM-LK frequencies and spleen-LK frequencies. (B) Compared with WT mice, JAK2V617F mice showed decreased nucleated cells in the femur, spleen, and body. Consequently, LSKs and LKs decreased in the femur, spleen, and body of recipients of JAK2V617F cells. Compared with JAK2V617F mice, double-mutant mice showed increased nucleated cells, LSKs, and LKs in the femur, spleen, and body, and double-mutant mice had comparable numbers of LSKs and LKs in the body as WT mice. (C) Compared with WT mice, TET2KD mice showed increased BM- and spleen-LSK frequencies, and JAK2V617F mice and double-mutant mice showed decreased spleen-LSK frequencies; TET2KD mice and double-mutant mice showed increased BM- and spleen-LK frequencies, and JAK2V617F mice showed increased spleen-LK frequencies. (D) Compared with WT mice, TET2KD mice showed increased nucleated cells in the spleen and body, and increased LSKs and LKs in the femur, spleen, and body; JAK2V617F mice showed increased LSKs and LKs in the spleen; double-mutant mice showed increased LSKs in the body and increased LKs in the femur, spleen, and body. Error bars represent standard deviation. *P < .05 and **P < .01 vs WT mice; †P < .05 and ††P < .01 vs JAK2V617F mice. In the bottom column, the gray bar represents the average cell number in whole BM, the black bar represents that in spleen, and the sum of both represents that in body.

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