Analyses of erythropoiesis from embryonic stem cell-CD34(+) and cord blood-CD34(+) cells reveal mechanisms for defective expansion and enucleation of embryomic stem cell-erythroid cells.
Analyses of erythropoiesis from embryonic stem cell-CD34(+) and cord blood-CD34(+) cells reveal mechanisms for defective expansion and enucleation of embryomic stem cell-erythroid cells.
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胚胎干细胞-CD34和脐带血-CD34细胞的红细胞生成分析揭示了胚胎干细胞-红系细胞扩增和去核缺陷的机制
DOI：
10.1111/jcmm.17263
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发表时间：
2022-04
影响因子：
5.3
通讯作者：
An X
中科院分区：
文献类型：
--
作者：
Wang S;Zhao H;Zhang H;Gao C;Guo X;Chen L;Lobo C;Yazdanbakhsh K;Zhang S;An X
体外产生的红细胞具有用于输血的潜力。人胚胎干细胞(ES)和诱导多能干细胞(IPS)具有无限的自我更新能力，是体外培养RBC的首选细胞来源。然而，ES/iPS来源的红系细胞的扩增有限，与脐带血(CB)或外周血(PB)来源的红细胞相比，ES/iPS来源的红细胞去核率较低，这一事实阻碍了它们的应用。为了解决这一问题，我们试图通过比较脐血CD34+细胞和ES CD34+细胞的体外红细胞生成谱来研究其潜在的机制。我们发现ES-CD34+细胞来源的红系细胞的有限扩增与红系祖细胞的细胞周期缺陷有关。在探讨ES-CD34+细胞来源的正染红细胞(ES-Oro)去核的细胞和分子机制时，我们发现ES-Oro的染色质浓缩程度低于CB-CD34+细胞来源的正染红细胞(CB-Oro)。在分子水平上，RNA-seq和atac-seq分析都表明，参与染色质修饰的途径在ES-Oro中下调。此外，与CB-Oro相比，ES-Oro中在染色质凝聚或/和去核过程中起重要作用的分子的表达水平显著降低。总之，我们的发现揭示了ES CD34+细胞来源的红系细胞有限扩增和受损去核的机制，并可能有助于提高干细胞体外产生红细胞的能力。
Red blood cells (RBCs) generated ex vivo have the potential to be used for transfusion. Human embryonic stem cells (ES) and induced pluripotent stem cells (iPS) possess unlimited self‐renewal capacity and are the preferred cell sources to be used for ex vivo RBC generation. However, their applications are hindered by the facts that the expansion of ES/iPS‐derived erythroid cells is limited and the enucleation of ES/iPS‐derived erythroblasts is low compared to that derived from cord blood (CB) or peripheral blood (PB). To address this, we sought to investigate the underlying mechanisms by comparing the in vitro erythropoiesis profiles of CB CD34+ and ES CD34+ cells. We found that the limited expansion of ES CD34+ cell‐derived erythroid cells was associated with defective cell cycle of erythroid progenitors. In exploring the cellular and molecular mechanisms for the impaired enucleation of ES CD34+ cell‐derived orthochromatic erythroblasts (ES‐ortho), we found the chromatin of ES‐ortho was less condensed than that of CB CD34+ cell‐derived orthochromatic erythroblasts (CB‐ortho). At the molecular level, both RNA‐seq and ATAC‐seq analyses revealed that pathways involved in chromatin modification were down‐regulated in ES‐ortho. Additionally, the expression levels of molecules known to play important role in chromatin condensation or/and enucleation were significantly lower in ES‐ortho compared to that in CB‐ortho. Together, our findings have uncovered mechanisms for the limited expansion and impaired enucleation of ES CD34+ cell‐derived erythroid cells and may help to improve ex vivo RBC production from stem cells.
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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：
5.2
作者：
Kim, William S.;Zhu, Yuhua;Deng, Qiming;Chin, Chee Jia;He, Chong Bin;Grieco, Amanda J.;Dravid, Gautam G.;Parekh, Chintan;Hollis, Roger P.;Lane, Timothy F.;Bouhassira, Eric E.;Kohn, Donald B.;Crooks, Gay M.
通讯作者：
Crooks, Gay M.
影响因子：
5.9
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
通讯作者：
Eto, Koji
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
4
作者：
Dias, Jessica;Gumenyuk, Marina;Slukvin, Igor I.
通讯作者：
Slukvin, Igor I.