. T2 W4 ~ D! U1 I/ T在同时发表在Stem Cells and Development期刊上的另一篇标题为“The universal 3D3 antibody of human PODXL is pluripotent cytotoxic, and identifies a residual population after extended differentiation of pluripotent stem cells”的论文中，针对一种与人iPSCs临床应用相关的问题，Hu和同事们报道了一种大有希望的解决方法。人iPSCs具有癌细胞一样的快速生长能力，因此人iPSCs衍生细胞移植物（HiPSC-based cell transplants）中掺杂单个HiPSC细胞将让病人受者有患上肿瘤的风险。此外，未完全分化的人iPSCs也被认为是致瘤性的。随着人iPSCs衍生的细胞疗法已经进入临床试验，还没有安全方法消除接受人iPSCs衍生细胞移植的病人患上肿瘤的风险。Hu的这项研究的目标就是开发出一种安全方法消除人iPSCs衍生细胞移植物中这些具有致瘤能力的细胞。他的实验室发现利用一种业已开发出的抗体靶向攻击人iPSCs的细胞表面蛋白PODXL，能够杀死多能性细胞。; U+ t: I& h4 r6 M) o1 {8 m
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论文作者写道，“我们认为这种抗体可能被用来清除用于细胞移植的人多能性干细胞衍生细胞中具有致瘤能力的多能性干细胞。” . [$ v/ J) k; `3 p, C - b! u, ^4 X$ I' ?9 |% S已知PODXL参与10多种不同的人类恶性肿瘤形成，而且据报道，它在肿瘤转移和浸润中发挥着作用。他的实验室有兴趣发现这种抗体是否能够杀死癌症病人中的其他恶性肿瘤细胞。 4 q- B( \& D, w: k6 |" m7 Q7 I2 e x3 f" o4 K, }9 q
Hu和同事们发现在人iPSCs中，PODXL具有较高的基因表达水平，而且当它们分化时，它下降表达。他们最近发现即便在延长分化后，残留的PODXL阳性细胞群体持续存在。Hu说，研究人iPSCs衍生细胞移植物中，这种残留的PODXL阳性细胞群体是比较迫切的。（生物谷 Bioon.com） * O# ]* w+ W) i3 R7 E ~4 d" p% f+ \9 ^
本文系生物谷原创编译整理，欢迎转载！点击 获取授权。更多资讯请下载生物谷APP。# _( K$ y2 c( M; X4 B$ _
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The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis# `* Q/ V" `9 j: W& [
0 E6 D% g6 |: q, [+ S0 idoi:10.1038/ncomms10869 - i' r. R' q6 Z) B1 l% D3 c# O 4 p3 c1 @7 _- @% Y/ ]; ZZhicheng Shao, Ruowen Zhang, Alireza Khodadadi-Jamayran, Bo Chen, Michael R. Crowley, Muhamad A. Festok, David K. Crossman, Tim M. Townes &Kejin Hu - j9 Y6 F' t( R: [3 ?" X/ A( R; ?7 ^& z3 I, l% S4 ]/ m
It is well known that both recipient cells and donor nuclei demonstrate a mitotic advantage as observed in the traditional reprogramming with somatic cell nuclear transfer (SCNT). However, it is not known whether a specific mitotic factor plays a critical role in reprogramming. Here we identify an isoform of human bromodomain-containing 3 (BRD3), BRD3R (BRD3 with Reprogramming activity), as a reprogramming factor. BRD3R positively regulates mitosis during reprogramming, upregulates a large set of mitotic genes at early stages of reprogramming, and associates with mitotic chromatin. Interestingly, a set of the mitotic genes upregulated by BRD3R constitutes a pluripotent molecular signature. The two BRD3 isoforms display differential binding to acetylated histones. Our results suggest a molecular interpretation for the mitotic advantage in reprogramming and show that mitosis may be a driving force of reprogramming. 1 N' ~ K8 ?- y! ]) I$ O4 p5 K( c A( F3 W
The universal 3D3 antibody of human PODXL is pluripotent cytotoxic, and identifies a residual population after extended differentiation of pluripotent stem cells 3 m) e" k! `% I$ t1 e I4 U9 V5 r2 H7 T4 l' g8 j
doi:10.1089/scd.2015.0321" h8 k1 u, A; @7 i. z. p
# Z% L4 p" d! p) l8 w0 NLei Kang, Chunping Yao, Alireza Khodadadi-Jamayran, Weihua Xu, Ruowen Zhang, Nilam Sanjib Banerjee, Chia-Wei Chang, Louise T Chow, Dr. Tim Townes, and Dr. Kejin Hu2 y; o7 n6 i" \% c6 q6 S9 b/ n5 X
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Podocalyxin-like protein (PODXL) is a member of CD34 family proteins. It is the protein that carries many posttranslational epitopes responsible for various pluripotent surface markers including TRA-1-60, TRA-1-81, GCTM2, GP200 and mAb84. However, PODXL has not attracted the attention of stem cell biologists. Here, we report several features of PODXL mRNA and protein in pluripotent stem cells. Similar to the modification-dependent pluripotent epitopes, PODXL transcripts and carrier protein are also features of pluripotency. PODXL is highly expressed in early human embryos from oocytes up to 4-cell stages. During reprogramming of human cells to pluripotency, in contrast to TRA-1-60 and TRA-1-81, PODXL is activated by KLF4 at a very early time of reprogramming. Although TRA-1-60 and TRA-1-81 are completely lost upon differentiation, a residual PODXL+ population exists even after extended differentiation and they were identified by the universal human PODXL epitope 3D3. Unlike TRA-1-60 and TRA-1-81 epitopes that are unique to primate PSCs, PODXL carrier protein can be used as a murine surface marker. Most importantly, antibody to 3D3 epitope causes massive necrosis and apoptosis of hPSCs. We suggest that 3D3 antibody could be employed to eliminate the tumorigenic pluripotent cells in hPSC-derived cells for cell transplantation.0 D) Q% h& c4 b8 Q1 d