Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells.
Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells.
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作者：
造血干细胞（HSC）的自我更新受内在和外在信号的调控。虽然已经发现了一些调节HSC自我更新的途径，但这些途径是否可以由可递送的生长因子触发以诱导HSC生长或再生在很大程度上仍然未知。在这里，我们表明，多效生长因子，一个神经突起生长因子，没有已知的功能，造血，有效地促进造血干细胞在体外扩增和造血干细胞在体内再生。用多效生长因子处理小鼠骨髓HSC引起培养物中长期再增殖HSC计数的显著增加，如在竞争性再增殖测定中所测量的。与输入细胞和经多效生长因子处理的培养物相比，用多效生长因子处理人脐带血CD 34 + CDCD 38 −Lin−细胞也显著增加了培养物中的严重联合免疫缺陷（SCID）-再生细胞计数。全身给药的多效生长因子照射小鼠引起骨髓干细胞和祖细胞在体内的显着扩增，表明多效生长因子是造血干细胞的再生生长因子。机制上，多效生长因子激活HSC中的磷酸肌醇3-激酶（PI 3 K）信号传导; PI 3 K或Notch信号传导的拮抗作用抑制培养物中多效生长因子介导的HSC扩增。我们确定了分泌的生长因子多效因子作为HSC扩增和再生的新调节因子
Hematopoietic stem cell (HSC) self-renewal is regulated by both intrinsic and extrinsic signals. Although some of the pathways that regulate HSC self-renewal have been uncovered, it remains largely unknown whether these pathways can be triggered by deliverable growth factors to induce HSC growth or regeneration. Here we show that pleiotrophin, a neurite outgrowth factor with no known function in hematopoiesis, efficiently promotes HSC expansion in vitro and HSC regeneration in vivo. Treatment of mouse bone marrow HSCs with pleiotrophin caused a marked increase in long-term repopulating HSC counts in culture, as measured in competitive repopulating assays. Treatment of human cord blood CD34+CDCD38−Lin− cells with pleiotrophin also substantially increased severe combined immunodeficient (SCID)-repopulating cell counts in culture, compared to input and cytokine-treated cultures. Systemic administration of pleiotrophin to irradiated mice caused a pronounced expansion of bone marrow stem and progenitor cells in vivo, indicating that pleiotrophin is a regenerative growth factor for HSCs. Mechanistically, pleiotrophin activated phosphoinositide 3-kinase (PI3K) signaling in HSCs; antagonism of PI3K or Notch signaling inhibited pleiotrophin-mediated expansion of HSCs in culture. We identify the secreted growth factor pleiotrophin as a new regulator of both HSC expansion and regeneration
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影响因子：
20.3
作者：
Chute, John P.;Muramoto, Garrett G.;Chao, Nelson J.
通讯作者：
Chao, Nelson J.
DOI：
10.1073/pnas.0603806103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Chute, John P.;Muramoto, Garrett G.;McDonnell, Donald P.
通讯作者：
McDonnell, Donald P.
DOI：
10.1073/pnas.0704366104
发表时间：
2007-06-26
影响因子：
11.1
作者：
Chang, Yunchao;Zuka, Masahiko;Deuel, Thomas F.
通讯作者：
Deuel, Thomas F.
影响因子：
46.9
作者：
Adams, Gregor B.;Martin, Roderick P.;Scadden, David T.
通讯作者：
Scadden, David T.
影响因子：
23.9
作者：
Hooper AT;Butler JM;Nolan DJ;Kranz A;Iida K;Kobayashi M;Kopp HG;Shido K;Petit I;Yanger K;James D;Witte L;Zhu Z;Wu Y;Pytowski B;Rosenwaks Z;Mittal V;Sato TN;Rafii S
通讯作者：
Rafii S