M. Ackermann, A functional perspective on phenotypic heterogeneity in microorganisms, Nat. Rev. Microbiol, vol.13, pp.497-508, 2015.

C. A. Aktipis, A. M. Boddy, G. Jansen, U. Hibner, M. E. Hochberg et al., Cancer across the tree of life: cooperation and cheating in multicellularity, Philos. Trans. R. Soc. Lond. B Biol. Sci, vol.370, 2015.
URL : https://hal.archives-ouvertes.fr/hal-02191687

E. M. De-francesco, F. Sotgia, and M. P. Lisanti, Cancer stem cells (CSCs): metabolic strategies for their identification and eradication, Biochem. J, vol.475, pp.1611-1634, 2018.

J. Degregory, Adaptive Oncogenesis: A New Understanding of How Cancer Evolves inside Us, 2018.

A. Dirkse, A. Golebiewska, T. Buder, P. V. Nazarov, A. Muller et al., Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment, Nat. Commun, vol.10, p.1787, 2019.

T. Domazet-loso, J. Brajkovic, and D. Tautz, A phylostratigraphy approach to uncover the genomic history of major adaptations in metazoan lineages, Trends Genet, vol.23, pp.533-539, 2007.

A. Dongre and R. A. Weinberg, New insights into the mechanisms of epithelialmesenchymal transition and implications for cancer, Nat. Rev. Mol. Cell Biol, vol.20, pp.69-84, 2019.

S. Efroni, R. Duttagupta, J. Cheng, H. Dehghani, D. J. Hoeppner et al., Global transcription in pluripotent embryonic stem cells, Cell Stem Cell, vol.2, pp.437-447, 2008.

S. Efroni, S. Melcer, M. Nissim-rafinia, and E. Meshorer, Stem cells do play with dice: a statistical physics view of transcription, Cell Cycle, vol.8, pp.43-48, 2009.

M. Egeblad, E. S. Nakasone, and Z. Werb, Tumors as organs: complex tissues that interface with the entire organism, Dev. Cell, vol.18, pp.884-901, 2010.

K. Featherstone, K. Hey, H. Momiji, A. V. Mcnamara, A. L. Patist et al., Spatially coordinated dynamic gene transcription in living pituitary tissue, vol.5, p.8494, 2016.

C. L. Fisher and A. G. Fisher, Chromatin states in pluripotent, differentiated, and reprogrammed cells, Curr. Opin. Genet. Dev, vol.21, pp.140-146, 2011.

W. A. Flavahan, E. Gaskell, and B. E. Bernstein, Epigenetic plasticity and the hallmarks of cancer, Science, vol.357, p.2380, 2017.

C. D. Folmes, P. P. Dzeja, T. J. Nelson, and A. Terzic, Metabolic plasticity in stem cell homeostasis and differentiation, Cell Stem Cell, vol.11, pp.596-606, 2012.

P. Friedl, Prespecification and plasticity: shifting mechanisms of cell migration, Curr. Opin. Cell Biol, vol.16, pp.14-23, 2004.

N. P. Gao, O. Gandrillon, A. Pá-ldi, U. Herbach, and R. Gunawan, Universality of cell differentiation trajectories revealed by a reconstruction of transcriptional uncertainty landscapes from single-cell transcriptomic data, 2020.

A. Gaspar-maia, A. Alajem, E. Meshorer, and M. Ramalho-santos, Open chromatin in pluripotency and reprogramming, Nat. Rev. Mol. Cell Biol, vol.12, pp.36-47, 2011.

R. A. Gatenby, S. Avdieiev, K. Y. Tsai, and J. S. Brown, Integrating genetic and nongenetic drivers of somatic evolution during carcinogenesis: the biplane model, Evol. Appl, vol.00, pp.1-9, 2020.

A. Giladi, F. Paul, Y. Herzog, Y. Lubling, A. Weiner et al., Single-cell characterization of haematopoietic progenitors and their trajectories in homeostasis and perturbed haematopoiesis, Nat. Cell Biol, vol.20, pp.836-846, 2018.

C. A. Gravenmier, M. Siddique, and R. A. Gatenby, Adaptation to stochastic temporal variations in intratumoral blood flow: the Warburg effect as a bet hedging strategy, Bull. Math. Biol, vol.80, pp.954-970, 2018.

R. K. Grosberg and R. R. Strathmann, The evolution of multicellularity: a minor major transition?, Annu. Rev. Ecol. Evol. Syst, vol.38, pp.621-654, 2007.

G. S. Gulati, S. S. Sikandar, D. J. Wesche, A. Manjunath, A. Bharadwaj et al., Single-cell transcriptional diversity is a hallmark of developmental potential, Science, vol.367, pp.405-411, 2020.

G. Guo, L. Pinello, X. Han, S. Lai, L. Shen et al., Serum-based culture conditions provoke gene expression variability in mouse embryonic stem cells as revealed by single-cell analysis, Cell Rep, vol.14, pp.956-965, 2016.

P. B. Gupta, C. M. Fillmore, G. Jiang, S. D. Shapira, K. Tao et al., Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells, Cell, vol.146, pp.633-644, 2011.

K. Hochedlinger, R. Blelloch, C. Brennan, Y. Yamada, M. Kim et al., Reprogramming of a melanoma genome by nuclear transplantation, Genes Dev, vol.18, pp.1875-1885, 2004.

S. R. Hough, A. L. Laslett, S. B. Grimmond, G. Kolle, and M. F. Pera, A continuum of cell states spans pluripotency and lineage commitment in human embryonic stem cells, PLoS One, vol.4, p.7708, 2009.

S. Huang, I. Ernberg, and S. Kauffman, Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective, Semin. Cell Dev. Biol, vol.20, pp.869-876, 2009.

G. Jenkinson, E. Pujadas, J. Goutsias, and A. P. Feinberg, Potential energy landscapes identify the information-theoretic nature of the epigenome, Nat. Genet, vol.49, pp.719-729, 2017.

N. Ji, T. C. Middelkoop, R. A. Mentink, M. C. Betist, S. Tonegawa et al., Feedback control of gene expression variability in the Caenorhabditis elegans Wnt pathway, Cell, vol.155, pp.869-880, 2013.

D. Jia, M. Lu, K. H. Jung, J. H. Park, L. Yu et al., Elucidating cancer metabolic plasticity by coupling gene regulation with metabolic pathways, Proc. Natl. Acad. Sci. U S A, vol.116, pp.3909-3918, 2019.

M. K. Jolly, B. Huang, M. Lu, S. A. Mani, H. Levine et al., Towards elucidating the connection between epithelial-mesenchymal transitions and stemness, J. R. Soc. Interface, vol.11, 2014.

T. Kalmar, C. Lim, P. Hayward, S. Munoz-descalzo, J. Nichols et al., Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells, PLoS Biol, vol.7, p.1000149, 2009.

P. A. Kenny and M. J. Bissell, Tumor reversion: correction of malignant behavior by microenvironmental cues, Int. J. Cancer, vol.107, pp.688-695, 2003.

A. Kinnaird, S. Zhao, K. E. Wellen, and E. D. Michelakis, Metabolic control of epigenetics in cancer, Nat. Rev. Cancer, vol.16, pp.694-707, 2016.

A. M. Klein, L. Mazutis, I. Akartuna, N. Tallapragada, A. Veres et al., Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells, Cell, vol.161, pp.1187-1201, 2015.

A. Kode, J. S. Manavalan, I. Mosialou, G. Bhagat, C. V. Rathinam et al., Leukaemogenesis induced by an activating betacatenin mutation in osteoblasts, Nature, vol.506, pp.240-244, 2014.

A. A. Kolodziejczyk, J. K. Kim, J. C. Tsang, T. Ilicic, J. Henriksson et al., Single cell RNA-sequencing of pluripotent states unlocks modular transcriptional variation, Cell Stem Cell, vol.17, pp.471-485, 2015.

O. Kotte, B. Volkmer, J. L. Radzikowski, and M. Heinemann, Phenotypic bistability in Escherichia coli's central carbon metabolism, Mol. Syst. Biol, vol.10, p.736, 2014.

R. M. Kumar, P. Cahan, A. K. Shalek, R. Satija, A. J. Daleykeyser et al., , 2014.

, Deconstructing transcriptional heterogeneity in pluripotent stem cells, Nature, vol.516, pp.56-61

G. Lee, R. R. Hall, A. , A. U. Levy, S. F. Ziv et al., Bet hedging in yeast by heterogeneous, agecorrelated expression of a stress protectant, J. Stem Cell Res. Ther, vol.6, p.1001325, 2012.

W. H. Lewis, Pinocytosis by malignant cells, Cancer Res, vol.29, pp.666-679, 1937.

Q. Li, A. Wennborg, E. Aurell, E. Dekel, J. Z. Zou et al., Dynamics inside the cancer cell attractor reveal cell heterogeneity, limits of stability, and escape, Proc. Natl. Acad. Sci. U S A, vol.113, pp.2672-2677, 2016.

M. Lu, M. K. Jolly, H. Levine, J. N. Onuchic, B. et al., MicroRNA-based regulation of epithelial-hybrid-mesenchymal fate determination, Proc. Natl. Acad. Sci. U S A, vol.110, pp.18144-18149, 2013.

B. D. Macarthur and I. R. Lemischka, , 2013.

, Statistical mechanics of pluripotency, Cell, vol.154, pp.484-489

B. D. Macarthur, A. Sevilla, M. Lenz, F. J. Muller, B. M. Schuldt et al., Nanog-dependent feedback loops regulate murine embryonic stem cell heterogeneity, Nat. Cell Biol, vol.14, pp.1139-1147, 2012.

M. V. Maffini, A. M. Soto, J. M. Calabro, A. A. Ucci, and C. Sonnenschein, The stroma as a crucial target in rat mammary gland carcinogenesis, J. Cell Sci, vol.117, pp.1495-1502, 2004.

I. Martincorena, A. Roshan, M. Gerstung, P. Ellis, P. Van-loo et al., Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin, Science, vol.348, pp.880-886, 2015.

E. Meshorer, D. Yellajoshula, E. George, P. J. Scambler, D. T. Brown et al., , 2006.

, Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells, Dev. Cell, vol.10, pp.105-116

T. Messmer, F. Von-meyenn, A. Savino, F. Santos, H. Mohammed et al., Transcriptional heterogeneity in naive and primed human pluripotent stem cells at single-cell resolution, Cell Rep, vol.26, pp.815-824, 2019.

R. E. Michod, R. , and D. , Cooperation and conflict in the evolution of multicellularity, Heredity (Edinb), vol.86, pp.1-7, 2001.

V. Moignard, S. Woodhouse, L. Haghverdi, A. J. Lilly, Y. Tanaka et al., Decoding the regulatory network of early blood development from single-cell gene expression measurements, Nat. Biotechnol, vol.33, pp.269-276, 2015.

A. Moussy, J. Cosette, R. Parmentier, C. Da-silva, G. Corre et al., Integrated time-lapse and single-cell transcription studies highlight the variable and dynamic nature of human hematopoietic cell fate commitment, e2001867. New, vol.15, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01934491

L. V. Nguyen, R. Vanner, P. Dirks, and C. J. Eaves, Cancer stem cells: an evolving concept, Nat. Rev. Cancer, vol.12, pp.133-143, 2012.

Q. H. Nguyen, S. W. Lukowski, H. S. Chiu, A. Senabouth, T. J. Bruxner et al., Single-cell RNA-seq of human induced pluripotent stem cells reveals cellular heterogeneity and cell state transitions between subpopulations, Genome Res, vol.28, pp.1053-1066, 2018.

A. Olsson, M. Venkatasubramanian, V. K. Chaudhri, B. J. Aronow, N. Salomonis et al., Single-cell analysis of mixedlineage states leading to a binary cell fate choice, Nature, vol.537, pp.698-702, 2016.

A. Paldi, Effects of the in vitro manipulation of stem cells: epigenetic mechanisms as mediators of induced metabolic fluctuations, Epigenomics, vol.5, pp.429-437, 2013.
URL : https://hal.archives-ouvertes.fr/hal-02881207

A. Pastore, F. Gaiti, S. X. Lu, R. M. Brand, S. Kulm et al., Corrupted coordination of epigenetic modifications leads to diverging chromatin states and transcriptional heterogeneity in CLL, Nat. Commun, vol.10, p.1874, 2019.

N. Pelaez, A. Gavalda-miralles, B. Wang, H. T. Navarro, H. Gudjonson et al., Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation, vol.4, p.8924, 2015.

T. Perestrelo, M. Correia, J. Ramalho-santos, and D. Wirtz, Metabolic and mechanical cues regulating pluripotent stem cell fate, Trends Cell Biol, vol.28, pp.1014-1029, 2018.

C. Pina, C. Fugazza, A. J. Tipping, J. Brown, S. Soneji et al., Inferring rules of lineage commitment in haematopoiesis, Nat. Cell Biol, vol.14, pp.287-294, 2012.

M. H. Raaijmakers, S. Mukherjee, S. Guo, S. Zhang, T. Kobayashi et al., Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia, Nature, vol.464, pp.852-857, 2010.

E. V. Ram and E. Meshorer, Transcriptional competence in pluripotency, Genes Dev, vol.23, pp.2793-2798, 2009.

A. Richard, L. Boullu, U. Herbach, A. Bonnafoux, V. Morin et al., Singlecell-based analysis highlights a surge in cell-tocell molecular variability preceding irreversible commitment in a differentiation process, PLoS Biol, vol.14, p.1002585, 2016.

A. C. Rios, B. D. Capaldo, F. Vaillant, B. Pal, R. Van-ineveld et al., Intraclonal plasticity in mammary tumors revealed through large-scale single-cell resolution 3D imaging, Cancer Cell, vol.35, pp.618-632, 2019.

H. Rubin, What keeps cells in tissues behaving normally in the face of myriad mutations?, Bioessays, vol.28, pp.515-524, 2006.

I. Sanchez-garcia, How tumour cell identity is established? Semin, Cancer Biol, vol.32, pp.1-2, 2015.

S. Semrau, J. E. Goldmann, M. Soumillon, T. S. Mikkelsen, R. Jaenisch et al., Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells, Nat. Commun, vol.8, p.1096, 2017.

M. L. Siegal, Shifting sugars and shifting paradigms, PLoS Biol, vol.13, 2015.

V. Snyder, T. C. Reed-newman, L. Arnold, S. M. Thomas, A. et al., Cancer stem cell metabolism and potential therapeutic targets, Front. Oncol, vol.8, p.203, 2018.

E. Solary and L. Lapane, The role of host environment in cancer evolution, Evol. Appl, vol.13, pp.1756-1770, 2020.

A. Solopova, J. Van-gestel, F. J. Weissing, H. Bachmann, B. Teusink et al., Bet-hedging during bacterial diauxic shift, Proc. Natl. Acad. Sci. U S A, vol.111, pp.7427-7432, 2014.

M. Spivakov and A. G. Fisher, Epigenetic signatures of stem-cell identity, Nat. Rev. Genet, vol.8, pp.263-271, 2007.

K. Sprouffske, L. M. Merlo, P. J. Gerrish, C. C. Maley, and P. D. Sniegowski, Cancer in light of experimental evolution, Curr. Biol, vol.22, pp.762-771, 2012.

D. E. Stange, B. K. Koo, M. Huch, G. Sibbel, O. Basak et al., , 2013.

, Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium, Cell, vol.155, pp.357-368

A. B. Stergachis, S. Neph, A. Reynolds, R. Humbert, B. Miller et al., Developmental fate and cellular maturity encoded in human regulatory DNA landscapes, Cell, vol.154, pp.888-903, 2013.

P. R. Tata, H. Mou, A. Pardo-saganta, R. Zhao, M. Prabhu et al., , 2013.

, Dedifferentiation of committed epithelial cells into stem cells in vivo, Nature, vol.503, pp.218-223

F. Thomas, B. Ujvari, F. Renaud, and M. Vincent, Cancer adaptations: atavism, de novo selection, or something in between?, Bioessays, vol.39, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02521509

M. E. Torres-padilla and I. Chambers, Transcription factor heterogeneity in pluripotent stem cells: a stochastic advantage, Development, vol.141, pp.2173-2181, 2014.

A. S. Trigos, R. B. Pearson, A. T. Papenfuss, and D. L. Goode, Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors, Proc. Natl. Acad. Sci. U S A, vol.114, pp.6406-6411, 2017.

A. S. Trigos, R. B. Pearson, A. T. Papenfuss, and D. L. Goode, How the evolution of multicellularity set the stage for cancer, Br. J. Cancer, vol.118, pp.145-152, 2018.

J. Trott, K. Hayashi, A. Surani, M. M. Babu, and A. Martinez-arias, Dissecting ensemble networks in ES cell populations reveals microheterogeneity underlying pluripotency, Mol. Biosyst, vol.8, pp.744-752, 2012.

A. R. Udyavar, D. J. Wooten, M. Hoeksema, M. Bansal, A. Califano et al., Novel hybrid phenotype revealed in small cell lung cancer by a transcription factor network model that can explain tumor heterogeneity, Cancer Res, vol.77, pp.1063-1074, 2017.

B. Ujvari, R. A. Gatenby, T. , and F. , The evolutionary ecology of transmissible cancers, Infect. Genet. Evol, vol.39, pp.293-303, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02515200

D. Van-dijk, R. Dhar, A. M. Missarova, L. Espinar, W. R. Blevins et al., , 2015.

, Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage, Nat. Commun, vol.6, p.7972

O. S. Venturelli, I. Zuleta, R. M. Murray, and H. El-samad, Population diversification in a yeast metabolic program promotes anticipation of environmental shifts, PLoS Biol, vol.13, p.1002042, 2015.

C. Vicente-duenas, J. Hauer, L. Ruiz-roca, D. Ingenhag, A. Rodriguez-meira et al., , 2015.

, Tumoral stem cell reprogramming as a driver of cancer: theory, biological models, implications in cancer therapy, Semin. Cancer Biol, vol.32, pp.3-9

M. Vincent, Cancer: a de-repression of a default survival program common to all cells?: a life-history perspective on the nature of cancer, Bioessays, vol.34, pp.72-82, 2012.

M. Vincent, Resistance to cancer chemotherapy as an atavism?, Bioessays, vol.38, p.1065, 2016.

C. R. Walkley, G. H. Olsen, S. Dworkin, S. A. Fabb, J. Swann et al., A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency, Cell, vol.129, pp.1097-1110, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00166246

J. Wang, E. Atolia, B. Hua, Y. Savir, R. Escalante-chong et al., Natural variation in preparation for nutrient depletion reveals a cost-benefit tradeoff, PLoS Biol, vol.13, p.1002041, 2015.

C. B. Ware, Concise review: lessons from naive human pluripotent cells, Stem Cells, vol.35, pp.35-41, 2017.

L. Weinberger, M. Ayyash, N. Novershtern, and J. H. Hanna, Dynamic stem cell states: naive to primed pluripotency in rodents and humans, Nat. Rev. Mol. Cell Biol, vol.17, pp.155-169, 2016.

O. Yanes, J. Clark, D. M. Wong, G. J. Patti, A. Sanchez-ruiz et al., Metabolic oxidation regulates embryonic stem cell differentiation, Nat. Chem. Biol, vol.6, pp.411-417, 2010.

V. T. Yerlici and L. F. Landweber, Programmed genome rearrangements in the ciliate oxytricha, Microbiol. Spectr, vol.2, p.10, 2014.

K. Yizhak, F. Aguet, J. Kim, J. M. Hess, K. Kubler et al., RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues, Science, vol.364, p.726, 2019.

A. Yokoyama, N. Kakiuchi, T. Yoshizato, Y. Nannya, H. Suzuki et al., Agerelated remodelling of oesophageal epithelia by mutated cancer drivers, Nature, vol.565, pp.312-317, 2019.

L. Yu, M. Lu, D. Jia, J. Ma, E. Ben-jacob et al., Modeling the genetic regulation of cancer metabolism: interplay between glycolysis and oxidative phosphorylation, Cancer Res, vol.77, pp.1564-1574, 2017.

J. Zhang, X. J. Tian, H. Zhang, Y. Teng, R. Li et al., TGFbeta-induced epithelial-to-mesenchymal transition proceeds through stepwise activation of multiple feedback loops, Sci. Signal, vol.7, p.91, 2014.