Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation

Isabel Ferreirós-Vidal; Thomas Carroll; Tianyi Zhang; Vincenzo Lagani; Ricardo N. Ramirez; Elizabeth Ing-Simmons; Alicia G. Gómez-Valadés; Lee Cooper; Ziwei Liang; Georgios Papoutsoglou; Gopuraja Dharmalingam; Ya Guo; Sonia Tarazona; Sunjay J. Fernandes; Peri Noori; Gilad Silberberg; Amanda G. Fisher; Ioannis Tsamardinos; Ali Mortazavi; Boris Lenhard; Ana Conesa; Jesper Tegner; Matthias Merkenschlager; David Gomez-Cabrero

doi:10.1371/journal.pbio.2006506

Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation

Isabel Ferreirós-Vidal, Thomas Carroll, Tianyi Zhang, Vincenzo Lagani, Ricardo N. Ramirez, Elizabeth Ing-Simmons, Alicia G. Gómez-Valadés, Lee Cooper, Ziwei Liang, Georgios Papoutsoglou, Gopuraja Dharmalingam, Ya Guo, Sonia Tarazona, Sunjay J. Fernandes, Peri Noori, Gilad Silberberg, Amanda G. Fisher, Ioannis Tsamardinos, Ali Mortazavi, Boris LenhardAna Conesa, Jesper Tegner, Matthias Merkenschlager, David Gomez-Cabrero

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6 Scopus citations

Abstract

The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage-specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type-specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell-progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.

Original language	English (US)
Pages (from-to)	e2006506
Journal	PLOS Biology
Volume	17
Issue number	4
DOIs	https://doi.org/10.1371/journal.pbio.2006506
State	Published - Apr 12 2019

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: EU FP7-Health STATegra project (grant number 36000). AG, VL, RR, AC, GP, ST, SF, PN, ME, JT, AM, MM, DGC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wellcome (grant number 099276/Z/12/Z). MM. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Medical Research Council, UK (grant number Institute Core Funding). AGF, BL, MM. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Bloodwise (grant number 09036). LC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wellcome (grant number). BL. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Research Council (grant number Repleniche). AGF. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Research Council (grant number 617393- CAUSALPATH). IT, VL, GP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MINECO (grant number BIO2015-71658-R). AC, ST. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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10.1371/journal.pbio.2006506

https://repository.kaust.edu.sa/bitstream/10754/652916/1/journal.pbio.2006506.pdf

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Ferreirós-Vidal, I., Carroll, T., Zhang, T., Lagani, V., Ramirez, R. N., Ing-Simmons, E., Gómez-Valadés, A. G., Cooper, L., Liang, Z., Papoutsoglou, G., Dharmalingam, G., Guo, Y., Tarazona, S., Fernandes, S. J., Noori, P., Silberberg, G., Fisher, A. G., Tsamardinos, I., Mortazavi, A., ... Gomez-Cabrero, D. (2019). Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation. PLOS Biology, 17(4), e2006506. https://doi.org/10.1371/journal.pbio.2006506

@article{c46715dbd40a4d99ae1995d9f62f8dbe,

title = "Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation",

abstract = "The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage-specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type-specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell-progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.",

author = "Isabel Ferreir{\'o}s-Vidal and Thomas Carroll and Tianyi Zhang and Vincenzo Lagani and Ramirez, {Ricardo N.} and Elizabeth Ing-Simmons and G{\'o}mez-Valad{\'e}s, {Alicia G.} and Lee Cooper and Ziwei Liang and Georgios Papoutsoglou and Gopuraja Dharmalingam and Ya Guo and Sonia Tarazona and Fernandes, {Sunjay J.} and Peri Noori and Gilad Silberberg and Fisher, {Amanda G.} and Ioannis Tsamardinos and Ali Mortazavi and Boris Lenhard and Ana Conesa and Jesper Tegner and Matthias Merkenschlager and David Gomez-Cabrero",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: EU FP7-Health STATegra project (grant number 36000). AG, VL, RR, AC, GP, ST, SF, PN, ME, JT, AM, MM, DGC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wellcome (grant number 099276/Z/12/Z). MM. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Medical Research Council, UK (grant number Institute Core Funding). AGF, BL, MM. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Bloodwise (grant number 09036). LC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wellcome (grant number). BL. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Research Council (grant number Repleniche). AGF. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Research Council (grant number 617393- CAUSALPATH). IT, VL, GP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MINECO (grant number BIO2015-71658-R). AC, ST. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",

year = "2019",

month = apr,

day = "12",

doi = "10.1371/journal.pbio.2006506",

language = "English (US)",

volume = "17",

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Ferreirós-Vidal, I, Carroll, T, Zhang, T, Lagani, V, Ramirez, RN, Ing-Simmons, E, Gómez-Valadés, AG, Cooper, L, Liang, Z, Papoutsoglou, G, Dharmalingam, G, Guo, Y, Tarazona, S, Fernandes, SJ, Noori, P, Silberberg, G, Fisher, AG, Tsamardinos, I, Mortazavi, A, Lenhard, B, Conesa, A, Tegner, J, Merkenschlager, M & Gomez-Cabrero, D 2019, 'Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation', PLOS Biology, vol. 17, no. 4, pp. e2006506. https://doi.org/10.1371/journal.pbio.2006506

TY - JOUR

T1 - Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation

AU - Ferreirós-Vidal, Isabel

AU - Carroll, Thomas

AU - Zhang, Tianyi

AU - Lagani, Vincenzo

AU - Ramirez, Ricardo N.

AU - Ing-Simmons, Elizabeth

AU - Gómez-Valadés, Alicia G.

AU - Cooper, Lee

AU - Liang, Ziwei

AU - Papoutsoglou, Georgios

AU - Dharmalingam, Gopuraja

AU - Guo, Ya

AU - Tarazona, Sonia

AU - Fernandes, Sunjay J.

AU - Noori, Peri

AU - Silberberg, Gilad

AU - Fisher, Amanda G.

AU - Tsamardinos, Ioannis

AU - Mortazavi, Ali

AU - Lenhard, Boris

AU - Conesa, Ana

AU - Tegner, Jesper

AU - Merkenschlager, Matthias

AU - Gomez-Cabrero, David

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: EU FP7-Health STATegra project (grant number 36000). AG, VL, RR, AC, GP, ST, SF, PN, ME, JT, AM, MM, DGC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wellcome (grant number 099276/Z/12/Z). MM. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Medical Research Council, UK (grant number Institute Core Funding). AGF, BL, MM. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Bloodwise (grant number 09036). LC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wellcome (grant number). BL. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Research Council (grant number Repleniche). AGF. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Research Council (grant number 617393- CAUSALPATH). IT, VL, GP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MINECO (grant number BIO2015-71658-R). AC, ST. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PY - 2019/4/12

Y1 - 2019/4/12

N2 - The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage-specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type-specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell-progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.

AB - The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage-specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type-specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell-progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.

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UR - http://www.scopus.com/inward/record.url?scp=85065217452&partnerID=8YFLogxK

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DO - 10.1371/journal.pbio.2006506

M3 - Article

C2 - 30978178

SN - 1545-7885

VL - 17

SP - e2006506

JO - PLOS Biology

JF - PLOS Biology

IS - 4

ER -

Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation

Abstract

Bibliographical note

UN SDGs

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