Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation

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Standard

Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation. / Yang, Zhenghao; Xu, Xiaochan; Gu, Chan; Li, Jun; Wu, Qihong; Ye, Can; Nielsen, Alexander Valentin; Mao, Lichao; Ye, Junqing; Bai, Ke; Guo, Fan; Tang, Chao; Zhao, Yang.

In: Communications Biology , Vol. 3, No. 1, 629, 30.10.2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Yang, Z, Xu, X, Gu, C, Li, J, Wu, Q, Ye, C, Nielsen, AV, Mao, L, Ye, J, Bai, K, Guo, F, Tang, C & Zhao, Y 2020, 'Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation', Communications Biology , vol. 3, no. 1, 629. https://doi.org/10.1038/s42003-020-01346-w

APA

Yang, Z., Xu, X., Gu, C., Li, J., Wu, Q., Ye, C., Nielsen, A. V., Mao, L., Ye, J., Bai, K., Guo, F., Tang, C., & Zhao, Y. (2020). Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation. Communications Biology , 3(1), [629]. https://doi.org/10.1038/s42003-020-01346-w

Vancouver

Yang Z, Xu X, Gu C, Li J, Wu Q, Ye C et al. Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation. Communications Biology . 2020 Oct 30;3(1). 629. https://doi.org/10.1038/s42003-020-01346-w

Author

Yang, Zhenghao ; Xu, Xiaochan ; Gu, Chan ; Li, Jun ; Wu, Qihong ; Ye, Can ; Nielsen, Alexander Valentin ; Mao, Lichao ; Ye, Junqing ; Bai, Ke ; Guo, Fan ; Tang, Chao ; Zhao, Yang. / Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation. In: Communications Biology . 2020 ; Vol. 3, No. 1.

Bibtex

@article{8c1b15fb2a40417f9ef43ac20330589e,
title = "Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation",
abstract = "Mouse somatic cells can be chemically reprogrammed into pluripotent stem cells (CiPSCs) through an intermediate extraembryonic endoderm (XEN)-like state. However, it is elusive how the chemicals orchestrate the cell fate alteration. In this study, we analyze molecular dynamics in chemical reprogramming from fibroblasts to a XEN-like state. We find that Sox17 is initially activated by the chemical cocktails, and XEN cell fate specialization is subsequently mediated by Sox17 activated expression of other XEN master genes, such as Sall4 and Gata4. Furthermore, this stepwise process is differentially regulated. The core reprogramming chemicals CHIR99021, 616452 and Forskolin are all necessary for Sox17 activation, while differently required for Gata4 and Sall4 expression. The addition of chemical boosters in different phases further improves the generation efficiency of XEN-like cells. Taken together, our work demonstrates that chemical reprogramming is regulated in 3 distinct {"}prime-specify-transit{"} phases initiated with endogenous Sox17 activation, providing a new framework to understand cell fate determination. Yang, Xu, Gu et al. demonstrate that activation of endogenous Sox17 pushes fibroblasts to an extraembryonic endoderm-like state in chemically induced reprogramming of somatic cells into stem cells. This study provides insights into how chemicals prime the transition of somatic cells into stem cells.",
keywords = "STEM-CELLS, MOUSE FIBROBLASTS, EPITHELIAL-CELLS, GENE-EXPRESSION, SOMATIC-CELLS, DIFFERENTIATION, CONVERSION, INDUCTION",
author = "Zhenghao Yang and Xiaochan Xu and Chan Gu and Jun Li and Qihong Wu and Can Ye and Nielsen, {Alexander Valentin} and Lichao Mao and Junqing Ye and Ke Bai and Fan Guo and Chao Tang and Yang Zhao",
year = "2020",
month = oct,
day = "30",
doi = "10.1038/s42003-020-01346-w",
language = "English",
volume = "3",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation

AU - Yang, Zhenghao

AU - Xu, Xiaochan

AU - Gu, Chan

AU - Li, Jun

AU - Wu, Qihong

AU - Ye, Can

AU - Nielsen, Alexander Valentin

AU - Mao, Lichao

AU - Ye, Junqing

AU - Bai, Ke

AU - Guo, Fan

AU - Tang, Chao

AU - Zhao, Yang

PY - 2020/10/30

Y1 - 2020/10/30

N2 - Mouse somatic cells can be chemically reprogrammed into pluripotent stem cells (CiPSCs) through an intermediate extraembryonic endoderm (XEN)-like state. However, it is elusive how the chemicals orchestrate the cell fate alteration. In this study, we analyze molecular dynamics in chemical reprogramming from fibroblasts to a XEN-like state. We find that Sox17 is initially activated by the chemical cocktails, and XEN cell fate specialization is subsequently mediated by Sox17 activated expression of other XEN master genes, such as Sall4 and Gata4. Furthermore, this stepwise process is differentially regulated. The core reprogramming chemicals CHIR99021, 616452 and Forskolin are all necessary for Sox17 activation, while differently required for Gata4 and Sall4 expression. The addition of chemical boosters in different phases further improves the generation efficiency of XEN-like cells. Taken together, our work demonstrates that chemical reprogramming is regulated in 3 distinct "prime-specify-transit" phases initiated with endogenous Sox17 activation, providing a new framework to understand cell fate determination. Yang, Xu, Gu et al. demonstrate that activation of endogenous Sox17 pushes fibroblasts to an extraembryonic endoderm-like state in chemically induced reprogramming of somatic cells into stem cells. This study provides insights into how chemicals prime the transition of somatic cells into stem cells.

AB - Mouse somatic cells can be chemically reprogrammed into pluripotent stem cells (CiPSCs) through an intermediate extraembryonic endoderm (XEN)-like state. However, it is elusive how the chemicals orchestrate the cell fate alteration. In this study, we analyze molecular dynamics in chemical reprogramming from fibroblasts to a XEN-like state. We find that Sox17 is initially activated by the chemical cocktails, and XEN cell fate specialization is subsequently mediated by Sox17 activated expression of other XEN master genes, such as Sall4 and Gata4. Furthermore, this stepwise process is differentially regulated. The core reprogramming chemicals CHIR99021, 616452 and Forskolin are all necessary for Sox17 activation, while differently required for Gata4 and Sall4 expression. The addition of chemical boosters in different phases further improves the generation efficiency of XEN-like cells. Taken together, our work demonstrates that chemical reprogramming is regulated in 3 distinct "prime-specify-transit" phases initiated with endogenous Sox17 activation, providing a new framework to understand cell fate determination. Yang, Xu, Gu et al. demonstrate that activation of endogenous Sox17 pushes fibroblasts to an extraembryonic endoderm-like state in chemically induced reprogramming of somatic cells into stem cells. This study provides insights into how chemicals prime the transition of somatic cells into stem cells.

KW - STEM-CELLS

KW - MOUSE FIBROBLASTS

KW - EPITHELIAL-CELLS

KW - GENE-EXPRESSION

KW - SOMATIC-CELLS

KW - DIFFERENTIATION

KW - CONVERSION

KW - INDUCTION

U2 - 10.1038/s42003-020-01346-w

DO - 10.1038/s42003-020-01346-w

M3 - Journal article

C2 - 33128002

VL - 3

JO - Communications Biology

JF - Communications Biology

SN - 2399-3642

IS - 1

M1 - 629

ER -

ID: 252039028