《自然》推出细胞重新编程设计指南（附原文）

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2 F4 U. a* x" ^% j9 @! O: B( R《自然》推出细胞重新编程设计指南9 p: E6 G- G9 t
来源：生物360 作者：koo
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本周的《自然》杂志报告了一种不同多功能细胞，可以变成几乎所有类型的细胞。这些研究结果属于一系列论文的集合，由宏伟计划团发表，揭示了重新编程细胞让其到达多功能状态的事件细节。理解这些事件给控制这些重新编程过程提供了基础，而且新颖的多功能细胞类型具有潜在的临床应用可能。
% ]: y. s1 l; D- w$ T通过强迫一些叫作转录因子的特定基因的表达，可以重新编程已经分化的成熟细胞，让其回到多功能状态，从而可以变成一系列不同的细胞类型。这种诱导多功能干细胞在个性化和再生医学领域大有希望。
* v3 H7 R6 Y" c, u+ v两篇由加拿大多伦多西乃山医院的Andras Nagy和研究团队发表的论文，发现了决定重新编程细胞结果的一系列事件的新细节，并且探讨了转录因子介导的重新编程细胞的其他结果。研究者观测到了一个新的多功能细胞类型，叫作F级细胞，因为这些细胞会形成外观毛茸茸的群落。这些细胞是稳定的，可能有助于它们在未来用于细胞治疗。
& u; v0 z; ~8 A$ q& g" ~1 [另外3篇论文发表在《自然—通讯》上，更加仔细地观察了多种在这样的条件下进行重新编程的细胞过程，例如影响诱导多功能性的分子事件，或者识别重新编程过程的蛋白质表达变化。以上这些研究揭示了细胞重新编程的新细节，并且提出了还存在其他细胞状态的可能，这些其他的细胞状态对于发展具有合适的再生医学和药物发现的人工细胞很可能是有用的。
/ F9 Z9 {! M% p; }0 Q  v原文检索：
$ o* K8 c" W% y9 u$ Z4 }$ @8 r0 d$ X# H6 ~Peter D. Tonge, Andrew J. Corso, Claudio Monetti, Samer M. I. Hussein, Mira C. Puri, Iacovos P. Michael, Mira Li, Dong-Sung Lee, Jessica C. Mar, Nicole Cloonan, David L. Wood, Maely E. Gauthier, Othmar Korn, Jennifer L. Clancy, Thomas Preiss, Sean M. Grimmond, Jong-Yeon Shin, Jeong-Sun Seo, Christine A. Wells, Ian M. Rogers & Andras Nagy. Divergent reprogramming routes lead to alternative stem-cell states. Nature, 10 December 2014; doi:10.1038/nature140478 m  c# e: V/ U* {
Samer M. I. Hussein, Mira C. Puri, Peter D. Tonge, Marco Benevento, Andrew J. Corso, Jennifer L. Clancy, Rowland Mosbergen, Mira Li, Dong-Sung Lee, Nicole Cloonan, David L. A. Wood, Javier Munoz, Robert Middleton, Othmar Korn, Hardip R. Patel, Carl A. White, Jong-Yeon Shin, Maely E. Gauthier, Kim-Anh Lê Cao, Jong-Il Kim, Jessica C. Mar, Nika Shakiba, William Ritchie, John E. J. Rasko, Sean M. Grimmond, Peter W. Zandstra, Christine A. Wells, Thomas Preiss, Jeong-Sun Seo, Albert J. R. Heck, Ian M. Rogers & Andras Nagy. Genome-wide characterization of the routes to pluripotency. Nature, 10 December 2014; doi:10.1038/nature14046

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  ~( h* h0 h4 k+ E: n转自Labome :【Nature communications三文推荐：细胞重编程过程中的蛋白组，表观遗传组和miRNA组动态改变】从分化的细胞重编程为全能干细胞，细胞内的蛋白组，表观遗传组和miRNA组发生了怎样的改变？请看Nature communications的三篇文章# ]$ t- H8 s8 x
Proteome adaptation in cell reprogramming proceeds via distinct transcriptional networks
$ }% C; S: A1 k0 t: {1 U( v$ S: jhttp://www.nature.com/ncomms/201 ... ull/ncomms6613.html4 f* x& W% _8 Z- ?
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The ectopic expression of ​Oct4, ​Klf4, ​c-Myc and ​Sox2 (OKMS) transcription factors allows reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). The reprogramming process, which involves a complex network of molecular events, is not yet fully characterized. Here we perform a quantitative mass spectrometry-based analysis to probe in-depth dynamic proteome changes during somatic cell reprogramming. Our data reveal defined waves of proteome resetting, with the first wave occurring 48 h after the activation of the reprogramming transgenes and involving specific biological processes linked to the ​c-Myc transcriptional network. A second wave of proteome reorganization occurs in a later stage of reprogramming, where we characterize the proteome of two distinct pluripotent cellular populations. In addition, the overlay of our proteome resource with parallel generated -omics data is explored to identify post-transcriptionally regulated proteins involved in key steps during reprogramming.2 g& ]! O- j' J! B
图1 : 蛋白质组学实验的原理概述工作流。5 k1 z" i! s# S6 U# S$ P

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An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator% ?5 {; [$ m; a  E! q
http://www.nature.com/ncomms/201 ... ull/ncomms6619.html. ?0 m0 ^8 M# ]0 m
Abstract
' ?, ]  F( r6 ZReprogramming of somatic cells to induced pluripotent stem cells involves a dynamic rearrangement of the epigenetic landscape. To characterize this epigenomic roadmap, we have performed MethylC-seq, ChIP-seq (H3K4/K27/K36me3) and RNA-Seq on samples taken at several time points during murine secondary reprogramming as part of Project Grandiose. We find that DNA methylation gain during reprogramming occurs gradually, while loss is achieved only at the ESC-like state. Binding sites of activated factors exhibit focal demethylation during reprogramming, while ESC-like pluripotent cells are distinguished by extension of demethylation to the wider neighbourhood. We observed that genes with ​CpG-rich promoters demonstrate stable low methylation and strong engagement of histone marks, whereas genes with ​CpG-poor promoters are safeguarded by methylation. Such DNA methylation-driven control is the key to the regulation of ESC-pluripotency genes, including ​Dppa4, ​Dppa5a and ​Esrrb. These results reveal the crucial role that DNA methylation plays as an epigenetic switch driving somatic cells to pluripotency., j' @( A$ k. ~* n3 C0 {, e# J

1 T9 v" j" I. c1 M# dSmall RNA changes en route to distinct cellular states of induced pluripotency+ _* n3 v3 E/ Q2 {, a1 z, D
http://www.nature.com/ncomms/201 ... ull/ncomms6522.html
0 L+ ^& x$ l1 }3 D: F# b6 u; sAbstract, ~: ~9 v% d+ ], l8 P+ G1 Z
MicroRNAs (miRNAs) are critical to somatic cell reprogramming into induced pluripotent stem cells (iPSCs), however, exactly how miRNA expression changes support the transition to pluripotency requires further investigation. Here we use a murine secondary reprogramming system to sample cellular trajectories towards iPSCs or a novel pluripotent ‘F-class’ state and perform small RNA sequencing. We detect sweeping changes in an early and a late wave, revealing that distinct miRNA milieus characterize alternate states of pluripotency. miRNA isoform expression is common but surprisingly varies little between cell states. Referencing other omic data sets generated in parallel, we find that miRNA expression is changed through transcriptional and post-transcriptional mechanisms. miRNA transcription is commonly regulated by dynamic histone modification, while DNA methylation/demethylation consolidates these changes at multiple loci. Importantly, our results suggest that a novel subset of distinctly expressed miRNAs supports pluripotency in the F-class state, substituting for miRNAs that serve such roles in iPSCs.
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bioon

An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator
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xiaostou

另外两篇原文有没有能提供的

bioon

Small RNA changes en route to distinct cellular states of induced pluripotency
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Nanaowan2014

Good News. However, there are still a lot to do.

bioon

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  f4 ^8 j& Q: k9 F/ N3 V& PProteome adaptation in cell reprogramming proceeds via distinct transcriptional networks
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