An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency

Junghyun Jo; Sohyun Hwang; Hyung Joon Kim; Soomin Hong; Jeoung Eun Lee; Sung Geum Lee; Ahmi Baek; Heonjong Han; Jin Il Lee; Insuk Lee; Dong Ryul Lee

doi:10.1093/nar/gkv1468

An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency

Junghyun Jo, Sohyun Hwang, Hyung Joon Kim, Soomin Hong, Jeoung Eun Lee, Sung Geum Lee, Ahmi Baek, Heonjong Han, Jin Il Lee, Insuk Lee, Dong Ryul Lee

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such asOct4,Sox2, Klf4 andMyc. Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 (Pc4), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes.

Original language	English
Pages (from-to)	1203-1215
Number of pages	13
Journal	Nucleic acids research
Volume	44
Issue number	3
DOIs	https://doi.org/10.1093/nar/gkv1468
Publication status	Published - 2016 Feb 18

Bibliographical note

Funding Information:
This research was partly supported by grants from the Bio and Medical Technology Development Program [2012M3A9C6049723] funded by the Ministry of Science, ICT and Future Planning, and Basic Science Research through the National Research Foundation ofKorea [2009- 0093821], the Stem Cell Research Program [2006-2004127 to D.L.], and grants from the National Research Foundation of Korea [2012M3A9B4028641, 2012M3A9C7050151 to I.L.]. Funding for open access charge: National Research Foundation of Korea.

Publisher Copyright:
© The Author(s) 2016.

All Science Journal Classification (ASJC) codes

Genetics

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10.1093/nar/gkv1468

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title = "An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency",

abstract = "Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such asOct4,Sox2, Klf4 andMyc. Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 (Pc4), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes.",

author = "Junghyun Jo and Sohyun Hwang and Kim, {Hyung Joon} and Soomin Hong and Lee, {Jeoung Eun} and Lee, {Sung Geum} and Ahmi Baek and Heonjong Han and Lee, {Jin Il} and Insuk Lee and Lee, {Dong Ryul}",

note = "Funding Information: This research was partly supported by grants from the Bio and Medical Technology Development Program [2012M3A9C6049723] funded by the Ministry of Science, ICT and Future Planning, and Basic Science Research through the National Research Foundation ofKorea [2009- 0093821], the Stem Cell Research Program [2006-2004127 to D.L.], and grants from the National Research Foundation of Korea [2012M3A9B4028641, 2012M3A9C7050151 to I.L.]. Funding for open access charge: National Research Foundation of Korea. Publisher Copyright: {\textcopyright} The Author(s) 2016.",

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doi = "10.1093/nar/gkv1468",

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AU - Jo, Junghyun

AU - Hwang, Sohyun

AU - Kim, Hyung Joon

AU - Hong, Soomin

AU - Lee, Jeoung Eun

AU - Lee, Sung Geum

AU - Baek, Ahmi

AU - Han, Heonjong

AU - Lee, Jin Il

AU - Lee, Insuk

AU - Lee, Dong Ryul

N1 - Funding Information: This research was partly supported by grants from the Bio and Medical Technology Development Program [2012M3A9C6049723] funded by the Ministry of Science, ICT and Future Planning, and Basic Science Research through the National Research Foundation ofKorea [2009- 0093821], the Stem Cell Research Program [2006-2004127 to D.L.], and grants from the National Research Foundation of Korea [2012M3A9B4028641, 2012M3A9C7050151 to I.L.]. Funding for open access charge: National Research Foundation of Korea. Publisher Copyright: © The Author(s) 2016.

PY - 2016/2/18

Y1 - 2016/2/18

N2 - Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such asOct4,Sox2, Klf4 andMyc. Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 (Pc4), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes.

AB - Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such asOct4,Sox2, Klf4 andMyc. Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 (Pc4), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes.

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An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency

Abstract

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