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单细胞转录谱揭示了人类诱导多能干细胞（hiPSCs）的异质性8 i* X6 i1 R* ~& \8 L
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人类诱导多能干细胞（hiPSCs）和人类胚胎干细胞（hESCs）是再生医学细胞来源的希望和候选。尽管hiPSCs和胚胎干细胞都具有分化为三胚层基本能力，然而二者在单细胞水平上的功能是否对等还有待证实。此外，干细胞群中，单细胞的异质性决定了重要单细胞的命运。在这里，我们使用单细胞分析，为362 个hiPSCs和hESCs绘制了基因表达图谱，解析了所特有的多能性和分化状态的42基因。与hESCs比较发现，单个hiPSCs在基因表达水平具有明显的异质性，这表明hiPSCs处于可选择的、不太稳定的多能性状态。 hiPSCs也显示了缓慢的生长动力学和受损的定向分化。我们的研究结果表明，在确定hiPSCs在多能性上等同于hESCs之前，我们应谨慎将hiPSCs分化产生的细胞用于再生医学。
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J Clin Invest. 2011 Mar 1;121(3):1217-21. doi: 10.1172/JCI44635. Epub 2011 Feb 7.# [8 J& y- o2 \" e9 J4 \% ~+ u' e/ [" M
C* ]( u) |2 E2 u0 M5 ~3 NSingle cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells2 K" e" R6 B* b. L
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Kazim H. Narsinh,1,2,3 Ning Sun,1,2 Veronica Sanchez-Freire,1,2 Andrew S. Lee,1,2
- V( m3 M5 Z( ~# Z! L- BPatricia Almeida,1,2 Shijun Hu,1,2 Taha Jan,4 Kitchener D. Wilson,1,2 Denise Leong,5
; T; i0 n H2 \3 qJarrett Rosenberg,2 Mylene Yao,5 Robert C. Robbins,6 and Joseph C. Wu1,2,4' u5 ?- |5 _8 G* S
+ }4 l$ M0 [2 h1Department of Medicine and 7 ^5 M7 F! m5 X, b; E% W4 N
2Department of Radiology, Stanford University School of Medicine, Stanford, California, USA.
, J+ M1 ]* n( `- `; `3University of California San Diego School of Medicine, La Jolla, California, USA.
2 k2 Z% y$ Q! V+ J1 C9 {5 s& m4Institute for Stem Cell Biology and Regenerative Medicine, 8 m0 k4 R' U% ]9 m
5Department of Obstetrics and Gynecology, and
1 o6 P0 s% {) a6Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California, USA.- U- c1 W- M. c
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Human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells(hESCs) are promising candidate cell sources for regenerative medicine. However, despite the common ability of hiPSCs and hESCs to differentiate into all 3 germ layers, their functional equivalence at the single cell level remains to be demonstrated. Moreover, single cell heterogeneity amongst stem cell populations may underlie important cell fate decisions. Here, we used single cell analysis to resolve the gene expression profiles of 362 hiPSCs and hESCs for an array of 42 genes that characterize the pluripotent and differentiated states. Comparison between single hESCs and single hiPSCs revealed markedly more heterogeneity in gene expression levels in the hiPSCs, suggesting that hiPSCs occupy an alternate, less stable pluripotentstate. hiPSCs also displayed slower growth kinetics and impaired directed differentiation as compared with hESCs. Our results suggest that caution should be exercised before assuming that hiPSCs occupy a pluripotent state equivalent to that of hESCs, particularly when producing differentiated cells for regenerative medicine aims.
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发表于 2011-3-17 17:20
发表于 2011-3-17 17:59
发表于 2011-3-17 21:39
