Unique molecular events during reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) at naïve state

Abstract
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Abstract

Derivation of human naïve cells in the ground state of pluripotency provides promising avenues for developmental biology studies and therapeutic manipulations. However, the molecular mechanisms involved in the establishment and maintenance of human naïve pluripotency remain poorly understood. Using the human inducible reprogramming system together with the 5iLAF naïve induction strategy, integrative analysis of transcriptional and epigenetic dynamics across the transition from human fibroblasts to naïve iPSCs revealed ordered waves of gene network activation sharing signatures with those found during embryonic development from late embryogenesis to pre-implantation stages. More importantly, Transcriptional analysis showed a significant transient reactivation of transcripts with 8-cell-stage-like characteristics in the late stage of reprogramming, suggesting transient activation of gene network with human zygotic genome activation (ZGA)-like signatures during the establishment of naïve pluripotency. Together, Dissecting the naïve reprogramming dynamics by integrative analysis improves the understanding of the molecular features involved in the generation of naïve pluripotency directly from somatic cells.

Data availability

The following data sets were generated

(2017) Integrative analysis of reprogramming human fibroblast cells to naïve pluripotency
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE89072).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89072

The following previously published data sets were used

(2015) Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE62777).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62777
1. Yan L
2. Yang M
3. Guo H
4. Yang L et al
(2013) Tracing pluripotency of human early embryos and embryonic stem cells by single cell RNA-seq
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE36552).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36552
1. Guo H
2. Zhu P
3. Yan L
4. Qiao J
5. Tang F
(2014) The DNA methylation landscape of human early embryos
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE49828).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49828

Article and author information

Author details

Yixuan Wang

School of Life Sciences and Technology, Tongji University, Shanghai, China

For correspondence
wangyixuan@tongji.edu.cn

Competing interests
The authors declare that no competing interests exist.
Chengchen Zhao

School of Life Sciences and Technology, Tongji University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Zhenzhen Hou

School of Life Sciences and Technology, Tongji University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Yuanyuan Yang

School of Life Sciences and Technology, Tongji University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Yan Bi

School of Life Sciences and Technology, Tongji University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Hong Wang

School of Life Sciences and Technology, Tongji University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Yong Zhang

School of Life Sciences and Technology, Tongji University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Shaorong Gao

School of Life Sciences and Technology, Tongji University, Shanghai, China

For correspondence
gaoshaorong@tongji.edu.cn

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1041-3928

Funding

National Natural Science Foundation of China (31671530)

Shaorong Gao

Ministry of Science and Technology of the People's Republic of China (2016YFA0100400)

Shaorong Gao

National Natural Science Foundation of China (31325019)

Shaorong Gao

National Natural Science Foundation of China (31471392)

Shaorong Gao

Ministry of Science and Technology of the People's Republic of China (2014CB964601)

Shaorong Gao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Human subjects: Human skin specimens from abortive fetus were obtained from the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University to make human embryonic fibroblasts (HEFs). The patients provided informed consent for tissue donations, and the Biological Research Ethics Committee of Tongji University approved the study.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.