Epigenomic analysis of multilineage differentiation of human embryonic stem cells

Wei Xie, Matthew D. Schultz, Ryan Lister, Zhonggang Hou, Nisha Rajagopal, Pradipta Ray, John W. Whitaker, Shulan Tian, R. David Hawkins, Danny Leung, Hongbo Yang, Tao Wang, Ah Young Lee, Scott A. Swanson, Jiuchun Zhang, Yun Zhu, Audrey Kim, Joseph R. Nery, Mark A. Urich, Samantha Kuan & 22 others Chia An Yen, Sarit Klugman, Pengzhi Yu, Kran Suknuntha, Nicholas E. Propson, Huaming Chen, Lee E. Edsall, Ulrich Wagner, Yan Li, Zhen Ye, Ashwinikumar Kulkarni, Zhenyu Xuan, Wen Yu Chung, Neil C. Chi, Jessica E. Antosiewicz-Bourget, Igor Slukvin, Ron Stewart, Michael Q. Zhang, Wei Wang, James A. Thomson, Joseph R. Ecker, Bing Ren

Research output: Contribution to journalArticle

368 Citations (Scopus)

Abstract

Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryonic development, we differentiated human embryonic stem cells into mesendoderm, neural progenitor cells, trophoblast-like cells, and mesenchymal stem cells and systematically characterized DNA methylation, chromatin modifications, and the transcriptome in each lineage. We found that promoters that are active in early developmental stages tend to be CG rich and mainly engage H3K27me3 upon silencing in nonexpressing lineages. By contrast, promoters for genes expressed preferentially at later stages are often CG poor and primarily employ DNA methylation upon repression. Interestingly, the early developmental regulatory genes are often located in large genomic domains that are generally devoid of DNA methylation in most lineages, which we termed DNA methylation valleys (DMVs). Our results suggest that distinct epigenetic mechanisms regulate early and late stages of ES cell differentiation.

Original languageEnglish (US)
Pages (from-to)1134-1148
Number of pages15
JournalCell
Volume153
Issue number5
DOIs
StatePublished - May 23 2013

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DNA Methylation
Stem cells
Epigenomics
Genes
Developmental Genes
Trophoblasts
Regulator Genes
Mesenchymal Stromal Cells
Transcriptome
Chromatin
Embryonic Development
Cell Differentiation
Stem Cells
Human Embryonic Stem Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Xie, W., Schultz, M. D., Lister, R., Hou, Z., Rajagopal, N., Ray, P., ... Ren, B. (2013). Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell, 153(5), 1134-1148. https://doi.org/10.1016/j.cell.2013.04.022
Xie, Wei ; Schultz, Matthew D. ; Lister, Ryan ; Hou, Zhonggang ; Rajagopal, Nisha ; Ray, Pradipta ; Whitaker, John W. ; Tian, Shulan ; Hawkins, R. David ; Leung, Danny ; Yang, Hongbo ; Wang, Tao ; Lee, Ah Young ; Swanson, Scott A. ; Zhang, Jiuchun ; Zhu, Yun ; Kim, Audrey ; Nery, Joseph R. ; Urich, Mark A. ; Kuan, Samantha ; Yen, Chia An ; Klugman, Sarit ; Yu, Pengzhi ; Suknuntha, Kran ; Propson, Nicholas E. ; Chen, Huaming ; Edsall, Lee E. ; Wagner, Ulrich ; Li, Yan ; Ye, Zhen ; Kulkarni, Ashwinikumar ; Xuan, Zhenyu ; Chung, Wen Yu ; Chi, Neil C. ; Antosiewicz-Bourget, Jessica E. ; Slukvin, Igor ; Stewart, Ron ; Zhang, Michael Q. ; Wang, Wei ; Thomson, James A. ; Ecker, Joseph R. ; Ren, Bing. / Epigenomic analysis of multilineage differentiation of human embryonic stem cells. In: Cell. 2013 ; Vol. 153, No. 5. pp. 1134-1148.
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abstract = "Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryonic development, we differentiated human embryonic stem cells into mesendoderm, neural progenitor cells, trophoblast-like cells, and mesenchymal stem cells and systematically characterized DNA methylation, chromatin modifications, and the transcriptome in each lineage. We found that promoters that are active in early developmental stages tend to be CG rich and mainly engage H3K27me3 upon silencing in nonexpressing lineages. By contrast, promoters for genes expressed preferentially at later stages are often CG poor and primarily employ DNA methylation upon repression. Interestingly, the early developmental regulatory genes are often located in large genomic domains that are generally devoid of DNA methylation in most lineages, which we termed DNA methylation valleys (DMVs). Our results suggest that distinct epigenetic mechanisms regulate early and late stages of ES cell differentiation.",
author = "Wei Xie and Schultz, {Matthew D.} and Ryan Lister and Zhonggang Hou and Nisha Rajagopal and Pradipta Ray and Whitaker, {John W.} and Shulan Tian and Hawkins, {R. David} and Danny Leung and Hongbo Yang and Tao Wang and Lee, {Ah Young} and Swanson, {Scott A.} and Jiuchun Zhang and Yun Zhu and Audrey Kim and Nery, {Joseph R.} and Urich, {Mark A.} and Samantha Kuan and Yen, {Chia An} and Sarit Klugman and Pengzhi Yu and Kran Suknuntha and Propson, {Nicholas E.} and Huaming Chen and Edsall, {Lee E.} and Ulrich Wagner and Yan Li and Zhen Ye and Ashwinikumar Kulkarni and Zhenyu Xuan and Chung, {Wen Yu} and Chi, {Neil C.} and Antosiewicz-Bourget, {Jessica E.} and Igor Slukvin and Ron Stewart and Zhang, {Michael Q.} and Wei Wang and Thomson, {James A.} and Ecker, {Joseph R.} and Bing Ren",
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Xie, W, Schultz, MD, Lister, R, Hou, Z, Rajagopal, N, Ray, P, Whitaker, JW, Tian, S, Hawkins, RD, Leung, D, Yang, H, Wang, T, Lee, AY, Swanson, SA, Zhang, J, Zhu, Y, Kim, A, Nery, JR, Urich, MA, Kuan, S, Yen, CA, Klugman, S, Yu, P, Suknuntha, K, Propson, NE, Chen, H, Edsall, LE, Wagner, U, Li, Y, Ye, Z, Kulkarni, A, Xuan, Z, Chung, WY, Chi, NC, Antosiewicz-Bourget, JE, Slukvin, I, Stewart, R, Zhang, MQ, Wang, W, Thomson, JA, Ecker, JR & Ren, B 2013, 'Epigenomic analysis of multilineage differentiation of human embryonic stem cells', Cell, vol. 153, no. 5, pp. 1134-1148. https://doi.org/10.1016/j.cell.2013.04.022

Epigenomic analysis of multilineage differentiation of human embryonic stem cells. / Xie, Wei; Schultz, Matthew D.; Lister, Ryan; Hou, Zhonggang; Rajagopal, Nisha; Ray, Pradipta; Whitaker, John W.; Tian, Shulan; Hawkins, R. David; Leung, Danny; Yang, Hongbo; Wang, Tao; Lee, Ah Young; Swanson, Scott A.; Zhang, Jiuchun; Zhu, Yun; Kim, Audrey; Nery, Joseph R.; Urich, Mark A.; Kuan, Samantha; Yen, Chia An; Klugman, Sarit; Yu, Pengzhi; Suknuntha, Kran; Propson, Nicholas E.; Chen, Huaming; Edsall, Lee E.; Wagner, Ulrich; Li, Yan; Ye, Zhen; Kulkarni, Ashwinikumar; Xuan, Zhenyu; Chung, Wen Yu; Chi, Neil C.; Antosiewicz-Bourget, Jessica E.; Slukvin, Igor; Stewart, Ron; Zhang, Michael Q.; Wang, Wei; Thomson, James A.; Ecker, Joseph R.; Ren, Bing.

In: Cell, Vol. 153, No. 5, 23.05.2013, p. 1134-1148.

Research output: Contribution to journalArticle

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T1 - Epigenomic analysis of multilineage differentiation of human embryonic stem cells

AU - Xie, Wei

AU - Schultz, Matthew D.

AU - Lister, Ryan

AU - Hou, Zhonggang

AU - Rajagopal, Nisha

AU - Ray, Pradipta

AU - Whitaker, John W.

AU - Tian, Shulan

AU - Hawkins, R. David

AU - Leung, Danny

AU - Yang, Hongbo

AU - Wang, Tao

AU - Lee, Ah Young

AU - Swanson, Scott A.

AU - Zhang, Jiuchun

AU - Zhu, Yun

AU - Kim, Audrey

AU - Nery, Joseph R.

AU - Urich, Mark A.

AU - Kuan, Samantha

AU - Yen, Chia An

AU - Klugman, Sarit

AU - Yu, Pengzhi

AU - Suknuntha, Kran

AU - Propson, Nicholas E.

AU - Chen, Huaming

AU - Edsall, Lee E.

AU - Wagner, Ulrich

AU - Li, Yan

AU - Ye, Zhen

AU - Kulkarni, Ashwinikumar

AU - Xuan, Zhenyu

AU - Chung, Wen Yu

AU - Chi, Neil C.

AU - Antosiewicz-Bourget, Jessica E.

AU - Slukvin, Igor

AU - Stewart, Ron

AU - Zhang, Michael Q.

AU - Wang, Wei

AU - Thomson, James A.

AU - Ecker, Joseph R.

AU - Ren, Bing

PY - 2013/5/23

Y1 - 2013/5/23

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AB - Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryonic development, we differentiated human embryonic stem cells into mesendoderm, neural progenitor cells, trophoblast-like cells, and mesenchymal stem cells and systematically characterized DNA methylation, chromatin modifications, and the transcriptome in each lineage. We found that promoters that are active in early developmental stages tend to be CG rich and mainly engage H3K27me3 upon silencing in nonexpressing lineages. By contrast, promoters for genes expressed preferentially at later stages are often CG poor and primarily employ DNA methylation upon repression. Interestingly, the early developmental regulatory genes are often located in large genomic domains that are generally devoid of DNA methylation in most lineages, which we termed DNA methylation valleys (DMVs). Our results suggest that distinct epigenetic mechanisms regulate early and late stages of ES cell differentiation.

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Xie W, Schultz MD, Lister R, Hou Z, Rajagopal N, Ray P et al. Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell. 2013 May 23;153(5):1134-1148. https://doi.org/10.1016/j.cell.2013.04.022