Stem Cell Reviews and Reports

, Volume 13, Issue 4, pp 532–541 | Cite as

Identifying Candidate Reprogramming Genes in Mouse Induced Pluripotent Stem Cells

  • Fang Gao
  • Jingyu Li
  • Heng Zhang
  • Xu Yang
  • Tiezhu An
Article

Abstract

Factor-based induced reprogramming approaches have tremendous potential for human regenerative medicine, but the efficiencies of these approaches are still low. In this study, we analyzed the global transcriptional profiles of mouse induced pluripotent stem cells (miPSCs) and mouse embryonic stem cells (mESCs) from seven different labs and present here the first successful clustering according to cell type, not by lab of origin. We identified 2131 different expression genes (DEs) as candidate pluripotency-associated genes by comparing mESCs/miPSCs with somatic cells and 720 DEs between miPSCs and mESCs. Interestingly, there was a significant overlap between the two DE sets. Therefore, we defined the overlap DEs as “consensus DEs” including 313 miPSC-specific genes expressed at a higher level in miPSCs versus mESCs and 184 mESC-specific genes in total and reasoned that these may contribute to the differences in pluripotency between mESCs and miPSCs. A classification of “consensus DEs” according to their different expression levels between somatic cells and mESCs/miPSCs shows that 86% of the miPSC-specific genes are more highly expressed in somatic cells, while 73% of mESC-specific genes are highly expressed in mESCs/miPSCs, indicating that the miPSCs have not efficiently silenced the expression pattern of the somatic cells from which they are derived and failed to completely induce the genes with high expression levels in mESCs. We further revealed a strong correlation between oocyte-enriched factors and insufficiently induced mESC-specific genes and identified 11 hub genes via network analysis. In light of these findings, we postulated that these key hub genes might not only drive somatic cell nuclear transfer (SCNT) reprogramming but also augment the efficiency and quality of miPSC reprogramming.

Keywords

Mouse embryonic stem cells Mouse induced pluripotent stem cells Oocyte-enrich factors Transcriptome Reprogramming 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China(J1210069).

Compliance with Ethical Standards

Conflict of Interest

The authors declare no competing financial interests.

Supplementary material

12015_2016_9704_MOESM1_ESM.psd (112 kb)
Supplementary Figure 1 Flow chart of dataset selection. (PSD 111 kb)
12015_2016_9704_MOESM2_ESM.docx (25 kb)
Supplementary Table 1 Microarray studies in cell reprogramming used for meta-analysis. (DOCX 25 kb)
12015_2016_9704_MOESM3_ESM.xlsx (123 kb)
Supplementary Table 2 The DEs list identified between stem cells and donor cells from meta-analysis. (XLSX 122 kb)
12015_2016_9704_MOESM4_ESM.xlsx (48 kb)
Supplementary Table 3 The DEs list identified between miPSCs and mESCs from meta-analysis. (XLSX 47 kb)
12015_2016_9704_MOESM5_ESM.xlsx (15 kb)
Supplementary Table 4 mESC-specific genes and miPSC-specific genes. (XLSX 15 kb)
12015_2016_9704_MOESM6_ESM.xlsx (418 kb)
Supplementary Table 5 The up-regulated genes in MII oocytes compared to MEFs. (XLSX 418 kb)
12015_2016_9704_MOESM7_ESM.xlsx (10 kb)
Supplementary Table 6 The primer sequences used for qPCR analysis of the hub genes. (XLSX 10 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Fang Gao
    • 1
    • 2
  • Jingyu Li
    • 2
    • 3
  • Heng Zhang
    • 2
  • Xu Yang
    • 2
  • Tiezhu An
    • 1
  1. 1.College of Life ScienceNortheast Forestry UniversityHarbinChina
  2. 2.College of Life ScienceNortheast Agricultural UniversityHarbinChina
  3. 3.Chong Qing Reproductive and Genetics InstituteChongqing Obstetrics and Gynecology HospitalChongqingChina

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