yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs

Stefan Frank; Gaurav Ahuja; Deniz Bartsch; Nicole Russ; Wenjie Yao; Joseph Chao-Chung Kuo; Jens-Peter Derks; Vijay Suresh Akhade; Yulia Kargapolova; Theodore Georgomanolis; Jan-Erik Messling; Marie Gramm; Lilija Brant; Rizwan Rehimi; Natalia Emilse Vargas; Alina Kuroczik; Tsun-Po Yang; Raja Ghazanfar Ali Sahito; Julia Franzen; Juergen Hescheler; Agapios Sachinidis; Martin Peifer; Alvaro Rada-Iglesias; Meena Kanduri; Ivan G Costa; Chandrasekhar Kanduri; Argyris Papantonis; Leo Kurian

doi:10.1016/j.stem.2018.11.005

yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs

Stefan Frank, Gaurav Ahuja, Deniz Bartsch, Nicole Russ, Wenjie Yao, Joseph Chao-Chung Kuo, Jens-Peter Derks, Vijay Suresh Akhade, Yulia Kargapolova, Theodore Georgomanolis, Jan-Erik Messling, Marie Gramm, Lilija Brant, Rizwan Rehimi, Natalia Emilse Vargas, Alina Kuroczik, Tsun-Po Yang, Raja Ghazanfar Ali Sahito, Julia Franzen, Juergen HeschelerAgapios Sachinidis, Martin Peifer, Alvaro Rada-Iglesias, Meena Kanduri, Ivan G Costa, Chandrasekhar Kanduri, Argyris Papantonis, Leo Kurian

19 Citations (Scopus)

Abstract

Human protein-coding genes are often accompanied by divergently transcribed non-coding RNAs whose functions, especially in cell fate decisions, are poorly understood. Using an hESC-based cardiac differentiation model, we define a class of divergent lncRNAs, termed yin yang lncRNAs (yylncRNAs), that mirror the cell-type-specific expression pattern of their protein-coding counterparts. yylncRNAs are preferentially encoded from the genomic loci of key developmental cell fate regulators. Most yylncRNAs are spliced polyadenylated transcripts showing comparable expression patterns in vivo in mouse and in human embryos. Signifying their developmental function, the key mesoderm specifier BRACHYURY (T) is accompanied by yylncT, which localizes to the active T locus during mesoderm commitment. yylncT binds the de novo DNA methyltransferase DNMT3B, and its transcript is required for activation of the T locus, with yylncT depletion specifically abolishing mesodermal commitment. Collectively, we report a lncRNA-mediated regulatory layer safeguarding embryonic cell fate transitions.

Original language	English
Journal	Cell Stem Cell
Volume	24
Issue number	2
Pages (from-to)	318-327.e8
ISSN	1934-5909
DOIs	https://doi.org/10.1016/j.stem.2018.11.005
Publication status	Published - 7 Feb 2019
Externally published	Yes

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Frank, S., Ahuja, G., Bartsch, D., Russ, N., Yao, W., Kuo, J. C-C., Derks, J-P., Akhade, V. S., Kargapolova, Y., Georgomanolis, T., Messling, J-E., Gramm, M., Brant, L., Rehimi, R., Vargas, N. E., Kuroczik, A., Yang, T-P., Sahito, R. G. A., Franzen, J., ... Kurian, L. (2019). yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs. Cell Stem Cell, 24(2), 318-327.e8. https://doi.org/10.1016/j.stem.2018.11.005

Frank, S, Ahuja, G, Bartsch, D, Russ, N, Yao, W, Kuo, JC-C, Derks, J-P, Akhade, VS, Kargapolova, Y, Georgomanolis, T, Messling, J-E, Gramm, M, Brant, L, Rehimi, R, Vargas, NE, Kuroczik, A, Yang, T-P, Sahito, RGA, Franzen, J, Hescheler, J, Sachinidis, A, Peifer, M, Rada-Iglesias, A, Kanduri, M, Costa, IG, Kanduri, C, Papantonis, A & Kurian, L 2019, 'yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs', Cell Stem Cell, vol. 24, no. 2, pp. 318-327.e8. https://doi.org/10.1016/j.stem.2018.11.005

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title = "yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs",

abstract = "Human protein-coding genes are often accompanied by divergently transcribed non-coding RNAs whose functions, especially in cell fate decisions, are poorly understood. Using an hESC-based cardiac differentiation model, we define a class of divergent lncRNAs, termed yin yang lncRNAs (yylncRNAs), that mirror the cell-type-specific expression pattern of their protein-coding counterparts. yylncRNAs are preferentially encoded from the genomic loci of key developmental cell fate regulators. Most yylncRNAs are spliced polyadenylated transcripts showing comparable expression patterns in vivo in mouse and in human embryos. Signifying their developmental function, the key mesoderm specifier BRACHYURY (T) is accompanied by yylncT, which localizes to the active T locus during mesoderm commitment. yylncT binds the de novo DNA methyltransferase DNMT3B, and its transcript is required for activation of the T locus, with yylncT depletion specifically abolishing mesodermal commitment. Collectively, we report a lncRNA-mediated regulatory layer safeguarding embryonic cell fate transitions.",

author = "Stefan Frank and Gaurav Ahuja and Deniz Bartsch and Nicole Russ and Wenjie Yao and Kuo, {Joseph Chao-Chung} and Jens-Peter Derks and Akhade, {Vijay Suresh} and Yulia Kargapolova and Theodore Georgomanolis and Jan-Erik Messling and Marie Gramm and Lilija Brant and Rizwan Rehimi and Vargas, {Natalia Emilse} and Alina Kuroczik and Tsun-Po Yang and Sahito, {Raja Ghazanfar Ali} and Julia Franzen and Juergen Hescheler and Agapios Sachinidis and Martin Peifer and Alvaro Rada-Iglesias and Meena Kanduri and Costa, {Ivan G} and Chandrasekhar Kanduri and Argyris Papantonis and Leo Kurian",

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T1 - yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs

AU - Frank, Stefan

AU - Ahuja, Gaurav

AU - Bartsch, Deniz

AU - Russ, Nicole

AU - Yao, Wenjie

AU - Kuo, Joseph Chao-Chung

AU - Derks, Jens-Peter

AU - Akhade, Vijay Suresh

AU - Kargapolova, Yulia

AU - Georgomanolis, Theodore

AU - Messling, Jan-Erik

AU - Gramm, Marie

AU - Brant, Lilija

AU - Rehimi, Rizwan

AU - Vargas, Natalia Emilse

AU - Kuroczik, Alina

AU - Yang, Tsun-Po

AU - Sahito, Raja Ghazanfar Ali

AU - Franzen, Julia

AU - Hescheler, Juergen

AU - Sachinidis, Agapios

AU - Peifer, Martin

AU - Rada-Iglesias, Alvaro

AU - Kanduri, Meena

AU - Costa, Ivan G

AU - Kanduri, Chandrasekhar

AU - Papantonis, Argyris

AU - Kurian, Leo

PY - 2019/2/7

Y1 - 2019/2/7

N2 - Human protein-coding genes are often accompanied by divergently transcribed non-coding RNAs whose functions, especially in cell fate decisions, are poorly understood. Using an hESC-based cardiac differentiation model, we define a class of divergent lncRNAs, termed yin yang lncRNAs (yylncRNAs), that mirror the cell-type-specific expression pattern of their protein-coding counterparts. yylncRNAs are preferentially encoded from the genomic loci of key developmental cell fate regulators. Most yylncRNAs are spliced polyadenylated transcripts showing comparable expression patterns in vivo in mouse and in human embryos. Signifying their developmental function, the key mesoderm specifier BRACHYURY (T) is accompanied by yylncT, which localizes to the active T locus during mesoderm commitment. yylncT binds the de novo DNA methyltransferase DNMT3B, and its transcript is required for activation of the T locus, with yylncT depletion specifically abolishing mesodermal commitment. Collectively, we report a lncRNA-mediated regulatory layer safeguarding embryonic cell fate transitions.

AB - Human protein-coding genes are often accompanied by divergently transcribed non-coding RNAs whose functions, especially in cell fate decisions, are poorly understood. Using an hESC-based cardiac differentiation model, we define a class of divergent lncRNAs, termed yin yang lncRNAs (yylncRNAs), that mirror the cell-type-specific expression pattern of their protein-coding counterparts. yylncRNAs are preferentially encoded from the genomic loci of key developmental cell fate regulators. Most yylncRNAs are spliced polyadenylated transcripts showing comparable expression patterns in vivo in mouse and in human embryos. Signifying their developmental function, the key mesoderm specifier BRACHYURY (T) is accompanied by yylncT, which localizes to the active T locus during mesoderm commitment. yylncT binds the de novo DNA methyltransferase DNMT3B, and its transcript is required for activation of the T locus, with yylncT depletion specifically abolishing mesodermal commitment. Collectively, we report a lncRNA-mediated regulatory layer safeguarding embryonic cell fate transitions.

U2 - 10.1016/j.stem.2018.11.005

DO - 10.1016/j.stem.2018.11.005

M3 - Journal article

C2 - 30554961

SN - 1934-5909

VL - 24

SP - 318-327.e8

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 2

ER -

yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs

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