SHIP is required for a functional hematopoietic stem cell niche
SHIP is required for a functional hematopoietic stem cell niche
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DOI：
10.1182/blood-2008-02-138008
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发表时间：
2009-03-26
期刊：
影响因子：
20.3
通讯作者：
Kerr, William G.
中科院分区：
文献类型：
--
作者：
Hazen, Amy L.;Smith, Michelle J.;Kerr, William G.
含SH 2结构域的肌醇5 '-磷酸酶-1（SHIP）缺乏显著增加骨髓（BM）中存在的造血干细胞（HSC）数量。然而，这些HSC的重建能力严重受损，表明SHIP表达可能是HSC功能的内在要求。为了进一步研究这个问题，我们开发了一个模型，其中SHIP表达在HSC中被消融，而它们驻留在SHIP活性环境中。在这种情况下，我们发现SHIP缺陷的HSC的长期再增殖不会受到影响。此外，来自该模型的SHIP缺陷型HSC在连续转移后以与野生型HSC相当的水平重新增殖。然而，当移植来自具有SHIP的全身消融的小鼠的HSC时，它们在功能上对于再增殖是受损的。这些发现表明，SHIP不是HSC功能的内在要求，而是BM环境支持功能胜任的HSC所需的SHIP。与这些发现相一致的是，构成BM小生境的细胞表达SHIP，而SHIP缺陷深刻地改变了它们的功能。（血。2009; 113：2924-2933）
SH2-domain-containing inositol 5'-phosphatase-1 (SHIP) deficiency significantly increases the number of hematopoietic stem cells (HSCs) present in the bone marrow (BM). However, the reconstitution capacity of these HSCs is severely impaired, suggesting that SHIP expression might be an intrinsic requirement for HSC function. To further examine this question, we developed a model in which SHIP expression is ablated in HSCs while they are resident in a SHIP-competent milieu. In this setting, we find that long-term repopulation by SHIP-deficient HSCs is not compromised. Moreover, SHIP-deficient HSCs from this model repopulate at levels comparable with wild-type HSCs upon serial transfer. However, when HSCs from mice with systemic ablation of SHIP are transplanted, they are functionally compromised for repopulation. These findings demonstrate that SHIP is not an intrinsic requirement for HSC function, but rather that SHIP is required for the BM milieu to support functionally competent HSCs. Consistent with these findings, cells that comprise the BM niche express SHIP and SHIP deficiency profoundly alters their function. (Blood. 2009; 113: 2924-2933)