近日，UCLA科学家们首次确定了在调节造血干细胞是如何再生(复制)中发挥关键作用的蛋白质。这一发现有助更好地理解这一蛋白质如何控制造血干细胞的生长和再生，并可能帮助找到更有效治疗多种血液系统疾病和癌症的方法。

这项研究发表在Journal of Clinical Investigation杂志上。造血干细胞(HSC)是造血细胞，具有自我更新和产生血液系统中所有类型细胞的能力。目前鲜为人知的是，造血干细胞移植达到人类骨髓后的再生(复制)过程。

在这项研究中，研究者发现细胞表面蛋白--蛋白酪氨酸磷酸酶-Sigma(PTP-Sigma)调节造血干细胞移植中的关键过程即造血干细胞再生，造血干细胞再生过程是关于造血干细胞怎么开始生长和在移植后如何生成健康的血细胞。

研究生第一作者Mamle Quarmyne表示：很多小鼠和人类造血干细胞生成(表达)PTP-Sigma。她还发现，PTP-Sigma基因缺失的小鼠，造血干细胞移植到小鼠中后再生能力明显增加。

在补充研究中，Quarmyne证实，不表达PTP-Sigma的人类血液造血干细胞导致HSC植入到移植免疫缺陷小鼠后的再生能力增长15倍。综上说述，这些研究表明，PTP-Sigma抑制正常HSC再生的能力，靶向阻断PTP-Sigma能基本上改善移植后小鼠和人体内HSC的再生能力。

Chute和同事进一步表明PTP-Sigma通过抑制蛋白RAC1来调节HSC再生功能，RAC1是公知的在移植后促进HSC再生的蛋白。

这些发现具有巨大的治疗潜能，因为我们已经确定造血干细胞的新受体PTP-Sigma，那么就可专门靶向作用以有力地提高患者接受移植后造血干细胞的再生。

这种方法还可潜在地加速接受化疗和/或辐射治疗患者的血液恢复。Chute的团队正与加州大学洛杉矶分校研究员合作开展研究工作，以测试小分子特异性抑制造血干细胞PTP- Sigma的能力。

原文链接：Protein tyrosine phosphatase–σ regulates hematopoietic stem cell–repopulating capacity

原文摘要：Hematopoietic stem cell (HSC) function is regulated by activation of receptor tyrosine kinases (RTKs). Receptor protein tyrosine phosphatases (PTPs) counterbalance RTK signaling; however, the functions of receptor PTPs in HSCs remain incompletely understood. We found that a receptor PTP, PTPσ, was substantially overexpressed in mouse and human HSCs compared with more mature hematopoietic cells. Competitive transplantation of bone marrow cells from PTPσ-deficient mice revealed that the loss of PTPσ substantially increased long-term HSC-repopulating capacity compared with BM cells from control mice. While HSCs from PTPσ-deficient mice had no apparent alterations in cell-cycle status, apoptosis, or homing capacity, these HSCs exhibited increased levels of activated RAC1, a RhoGTPase that regulates HSC engraftment capacity. shRNA-mediated silencing of PTPσ also increased activated RAC1 levels in wild-type HSCs. Functionally, PTPσ-deficient BM cells displayed increased cobblestone area–forming cell (CAFC) capacity and augmented transendothelial migration capacity, which was abrogated by RAC inhibition. Specific selection of human cord blood CD34+CD38–CD45RA–lin– PTPσ– cells substantially increased the repopulating capacity of human HSCs compared with CD34+CD38–CD45RA–lin– cells and CD34+CD38–CD45RA–lin–PTPσ+ cells. Our results demonstrate that PTPσ regulates HSC functional capacity via RAC1 inhibition and suggest that selecting for PTPσ-negative human HSCs may be an effective strategy for enriching human HSCs for transplantation.

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