Immortalization of erythroblasts by c-MYC and BCL-XL enables large-scale erythrocyte production from human pluripotent stem cells.
Immortalization of erythroblasts by c-MYC and BCL-XL enables large-scale erythrocyte production from human pluripotent stem cells.
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DOI：
10.1016/j.stemcr.2013.10.010
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发表时间：
2013
影响因子：
5.9
通讯作者：
Eto, Koji
中科院分区：
文献类型：
--
作者：
Hirose, Sho-ichi;Takayama, Naoya;Nakamura, Sou;Nagasawa, Kazumichi;Ochi, Kiyosumi;Hirata, Shinji;Yamazaki, Satoshi;Yamaguchi, Tomoyuki;Otsu, Makoto;Sano, Shinya;Takahashi, Nobuyasu;Sawaguchi, Akira;Ito, Mamoru;Kato, Takashi;Nakauchi, Hiromitsu;Eto, Koji
由于缺乏对红细胞自我复制机制的了解，使得体外大量生成红细胞变得困难。我们表明，c-MYC和BCL-XL转导到多能造血祖细胞来源于多能干细胞和基因过表达，使血型糖蛋白A+成红细胞，我们称之为永生化的红细胞祖细胞（imERYPC）的持续指数自我复制。在诱导型表达系统中，关闭c-MYC和BCL-XL的过表达使imERYPC成熟，染色质浓缩和细胞大小减少，血红蛋白合成，GCN 5下调，GATA 1上调，内源性BCL-XL和RAF 1，所有这些似乎都重现了正常的红细胞生成。imERYPC在体外和输注后免疫缺陷小鼠的循环中大多显示胎儿型血红蛋白和正常的氧解离。使用关键因素诱导imERYPC提供了一种红细胞生物发生的模型，可能有助于稳定供应供者非依赖性输血的红细胞。永生型成红细胞是通过c-MYC和BCL-XL的过表达建立的。基因关闭后，imERYPC在体外分化为成熟的成红细胞。imERYPC衍生的成熟细胞显示出与正常RBC相似的氧输送能力。无核细胞显示出免疫缺陷小鼠的循环潜力。在基因关闭后，imERYPCs重现了正常的红细胞分化，并显示出体外携氧能力和体内循环潜力。imERYPC为研究红细胞生成提供了一个平台，可能有助于输血用红细胞的稳定供应。
The lack of knowledge about the mechanism of erythrocyte biogenesis through self-replication makes the in vitro generation of large quantities of cells difficult. We show that transduction of c-MYC and BCL-XL into multipotent hematopoietic progenitor cells derived from pluripotent stem cells and gene overexpression enable sustained exponential self-replication of glycophorin A+ erythroblasts, which we term immortalized erythrocyte progenitor cells (imERYPCs). In an inducible expression system, turning off the overexpression of c-MYC and BCL-XL enabled imERYPCs to mature with chromatin condensation and reduced cell size, hemoglobin synthesis, downregulation of GCN5, upregulation of GATA1, and endogenous BCL-XL and RAF1, all of which appeared to recapitulate normal erythropoiesis. imERYPCs mostly displayed fetal-type hemoglobin and normal oxygen dissociation in vitro and circulation in immunodeficient mice following transfusion. Using critical factors to induce imERYPCs provides a model of erythrocyte biogenesis that could potentially contribute to a stable supply of erythrocytes for donor-independent transfusion. Immortalized-type erythroblasts are established by overexpression of c-MYC and BCL-XL After genes are turned off, imERYPCs differentiate into mature erythroblasts in vitro ImERYPC-derived mature cells show oxygen delivery capability similar to normal RBCs Enucleated cells reveal circulation potential in immune-deficient mice Takayama, Eto, and colleagues succeeded in generating immortalized erythrocyte progenitor cells (imERYPCs) from human PSCs. After genes were turned off, imERYPCs recapitulated normal erythrocyte differentiation and showed oxygen carrying capacity in vitro and circulation potential in vivo. imERYPCs provide a platform to study erythropoiesis, potentially contributing to a stable supply of erythrocytes for transfusion.
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影响因子：
3.7
作者：
Kurita R;Suda N;Sudo K;Miharada K;Hiroyama T;Miyoshi H;Tani K;Nakamura Y
通讯作者：
Nakamura Y
影响因子：
4.9
作者：
Belen Jimenez-Diaz, Maria;Mulet, Teresa;Angulo-Barturen, Inigo
通讯作者：
Angulo-Barturen, Inigo
DOI：
10.1073/pnas.0802220105
发表时间：
2008-09-02
影响因子：
11.1
作者：
Ma, Feng;Ebihara, Yasuhiro;Tsuji, Kohichiro
通讯作者：
Tsuji, Kohichiro
影响因子：
44.1
作者：
通讯作者：
--
影响因子：
20.3
作者：
Keerthivasan, Ganesan;Small, Sara;Crispino, John D.
通讯作者：
Crispino, John D.