OSKM诱导多能干细胞基因表达机制鉴定：早期见解

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本文研究论文深入探讨了"OCT4、SOX2、KLF4和MYC (OSKM)诱导的多能干细胞的基因表达：潜在机制的鉴定"。这项研究的背景是，科学家们已经发现通过外源性表达这四种转录因子，如Oct4、Sox2、Klf4和Myc，可以将体细胞重新编程为诱导多能干细胞 (iPSCs)，这一过程对于理解细胞命运转换和再生医学具有重要意义。研究方法部分，研究人员从NCBI的GEO数据库获取了GSE28688，其中包含了对照数据——未经处理的人类新生儿皮肤纤维母细胞 (HFF1)，以及在OSKM病毒转导后不同时间点（24小时、48小时和72小时）的诱导状态HFF1，两种iPSC细胞系，以及两种胚胎干细胞 (ES) 细胞系。为了识别在细胞重编程过程中差异表达的基因 (DEGs)，研究者使用了Limma包进行生物信息学分析，通过对比这些细胞类型的基因表达模式。随后，他们利用DAVID工具进行了 Kyoto Encyclopedia of Genes and Genomes (KEGG) 通路富集分析，以确定哪些生物学过程或信号通路可能在OSKM诱导的多能化过程中起关键作用。通过STRING数据库，构建了蛋白质-蛋白质相互作用 (PPI) 网络，进一步揭示了这些基因之间可能存在的调控关系。此外，研究者运用FastNetw等软件工具来计算和构建转录因子 (TFs) 的活性和调控网络，这有助于揭示OSKM诱导多能性过程中TFs的作用模式和潜在的调控机制。通过这些分析，论文作者试图揭示早期诱导多能性发生的分子机制，这对于优化iPS细胞制备技术，以及理解细胞命运决定和再生医学疗法的潜力具有重要价值。这篇研究论文提供了关于OSKM诱导多能干细胞基因表达的关键见解，包括DEGs的识别、功能通路的解读以及TFs的调控网络，为未来在干细胞研究和临床应用领域的进一步探索奠定了基础。

RES E AR C H Open Access

Gene expression of OCT4, SOX2, KLF4 and MYC

(OSKM) induced pluripotent stem cells:

identification for potential mechanisms

Yanning Cai

1,2*

, Xianhua Dai

1,2*

, Qianhua Zhang

1,2

and Zhiming Dai

1,2

Abstract

Background: Somatic cells could be reprogrammed to induced pluripotent stem cells (iPS) by ectopic expression

of OCT4, SOX2, KLF4 and MYC (OSKM). We aimed to gain insights into the early mechanisms underlying the

induction of pluripotency.

Methods: GSE28688 containing 14 gene expression profiles were downloaded from GEO, including untreated

human neonatal foreskin fibroblasts (HFF1) as control, OSKM-induced HFF1 (at 24, 48, 72 h post-transduction of

OSKM encoding viruses), two iPS cell lines, and two embryonic stem (ES) cell lines. Differentially expressed genes

(DEGs) were screened between different cell lines and the control by Limma package in Bioconductor. KEGG pathway

enrichment analysis was performed by DAVID. The STRING database was used to construct protein-protein interaction

(PPI) network. Activities and regulatory networks of transcription factors (TFs) were calculated and constructed by Fast

Network Component Analysis (FastNCA).

Results: Compared with untreated HFF1, 117, 347, 557, 2263 and 2307 DEGs were obtained from three point

post-transduction HFF1, iPS and ES cells. Meanwhile, up-regulated DEGs in first two days of HFF1 were mainly

enriched in RIG-I-like receptor (RLR) and Toll-like r eceptor (TLR) signaling pathways. D own-regulated DEGs at

72 h were significantly enriched in focal adhesion pathw ay w hich was similar to iPS cells. Moreover, ISG15, IRF7,

STAT1 and DDX58 were with higher degree in PPI networks during time series. Furthermore, the targets of six

selected TFs were mainly enriched in screened DEGs.

Conclusion: In this study, screened DEGs including ISG15, IRF7 and CCL5 participated in OSKM-induced pluripotency

might attenuate immune response post-transduction through RLR and TLR signaling pathways.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/

2503890341543007.

Keywords: Reprogramming, Transcriptional factor, Protein-protein interaction network, Regulatory network

Background

Human embryonic stem (ES) cells have potential in cell

replacement therapies using their regenerative proper-

ties. Disappointingly, there were many limitations for

using of ES cells as therapeutic transplantation material,

such as rejection [1], the risk of teratoma formation

from residual ES cells [2] and inadequate cell number

[3]. In contrast, induced pluripotent stem (iPS) cells take

advantages over ES cells. It is important to highlight the

need to investigate differences between iPS and ES cells.

In adult tissues and organs, fully differentiated cells

rarely change from one type to another. However, som-

atic cells can be forcibly reprogrammed to pluripotency

by cell fusion, somatic cell nuclear transfer and ectopic

expression of defined factors including octamer binding

transcription factor 4 (OCT4), SRY related high mobility

group box protein 2 (SOX 2), Kruppel like factor 4

(KLF4) and myelocytomatosis viral oncogene (MYC)

(known as OSKM factors) [4-6]. Takahashi and Yamanaka

* Correspondence: caiyanningmitl@sina.com ; issdxh@mail.sysu.edu.cn

School of Information Science and Technology, Sun Yat-sen University,

Higher Education Mega Center, No.132 East Outer Ring Road, Guangzhou,

China

SYSU-CMU Shunde International Joint Research Institute (JRI), Shunde,

Guangdong, China

Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and

reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain

Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,

unless otherwise stated.

Cai et al. Diagnostic Pathology (2015) 10:35

DOI 10.1186/s13000-015-0263-7

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