L. Ligue-contre-le-cancer, Grand Ouest) We thank K Riabowol for providing ING1 antibody and for his careful reading of the manuscript

A. Uccelli, L. Moretta, and V. Pistoia, Mesenchymal stem cells in health and disease, Nature Reviews Immunology, vol.2, issue.9, pp.726-736, 2008.
DOI : 10.1038/nri2395

C. Ménard and K. Tarte, Immunoregulatory properties of clinical grade mesenchymal stromal cells: evidence, uncertainties, and clinical application, Stem Cell Research & Therapy, vol.4, issue.3, p.64, 2013.
DOI : 10.1016/j.mayocp.2012.04.014

W. Wagner, P. Horn, M. Castoldi, A. Diehlmann, S. Bork et al., Replicative Senescence of Mesenchymal Stem Cells: A Continuous and Organized Process, PLoS ONE, vol.43, issue.5, p.2213, 2008.
DOI : 10.1371/journal.pone.0002213.t002

C. Fehrer, R. Brunauer, G. Laschober, H. Unterluggauer, S. Reitinger et al., Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan, Aging Cell, vol.39, issue.6, pp.745-757, 2007.
DOI : 10.1111/j.1474-9726.2007.00336.x

A. Mohyeldin, T. Garzón-muvdi, and A. Quiñones-hinojosa, Oxygen in Stem Cell Biology: A Critical Component of the Stem Cell Niche, Cell Stem Cell, vol.7, issue.2, pp.150-161, 2010.
DOI : 10.1016/j.stem.2010.07.007

S. Palomäki, M. Pietilä, S. Laitinen, J. Pesälä, R. Sormunen et al., HIF-1?? is upregulated in human mesenchymal stem cells, STEM CELLS, vol.106, issue.9, pp.1902-1909, 2013.
DOI : 10.1002/stem.1435

C. Tsai, Y. Chen, T. Yew, L. Chen, J. Wang et al., Hypoxia inhibits senescence and maintains mesenchymal stem cell properties through down-regulation of E2A-p21 by HIF-TWIST, Blood, vol.117, issue.2, pp.459-469, 2011.
DOI : 10.1182/blood-2010-05-287508

C. Guérillon, D. Larrieu, and R. Pedeux, ING1 and ING2: multifaceted tumor suppressor genes, Cellular and Molecular Life Sciences, vol.7, issue.8, pp.3753-3772, 2013.
DOI : 10.1007/s00018-013-1270-z

G. Tallen, S. Farhangi, M. Tamannai, N. Holtkamp, D. Mangoldt et al., The Inhibitor of Growth 1 (ING1) Proteins Suppress Angiogenesis and Differentially Regulate Angiopoietin Expression in Glioblastoma Cells, Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, vol.18, issue.2, pp.95-105, 2009.
DOI : 10.3727/096504009789954645

M. Blagosklonny, W. An, L. Romanova, J. Trepel, T. Fojo et al., p53 Inhibits Hypoxia-inducible Factor-stimulated Transcription, Journal of Biological Chemistry, vol.273, issue.20, pp.11995-11998, 1998.
DOI : 10.1074/jbc.273.20.11995

M. Kaluzová, S. Kaluz, M. I. Lerman, and E. J. Stanbridge, DNA Damage Is a Prerequisite for p53-Mediated Proteasomal Degradation of HIF-1?? in Hypoxic Cells and Downregulation of the Hypoxia Marker Carbonic Anhydrase IX, Molecular and Cellular Biology, vol.24, issue.13, pp.5757-5766, 2004.
DOI : 10.1128/MCB.24.13.5757-5766.2004

A. Ozer, L. C. Wu, and R. Bruick, The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF), Proceedings of the National Academy of Sciences, vol.102, issue.21, pp.7481-7486, 2005.
DOI : 10.1073/pnas.0502716102

M. Strioga, S. Viswanathan, A. Darinskas, O. Slaby, and J. Michalek, Same or Not the Same? Comparison of Adipose Tissue-Derived Versus Bone Marrow-Derived Mesenchymal Stem and Stromal Cells, Stem Cells and Development, vol.21, issue.14, pp.2724-2752, 2012.
DOI : 10.1089/scd.2011.0722

M. Garate, E. I. Campos, J. A. Bush, H. Xiao, and G. Li, Phosphorylation of the tumor suppressor p33ING1b at Ser-126 influences its protein stability and proliferation of melanoma cells, The FASEB Journal, vol.21, issue.13, pp.3705-3716, 2007.
DOI : 10.1096/fj.07-8069com

S. Satpathy, C. Guérillon, T. Kim, N. Bigot, S. Thakur et al., SUMOylation of the ING1b tumor suppressor regulates gene transcription, Carcinogenesis, vol.35, issue.10, pp.2214-2223, 2014.
DOI : 10.1093/carcin/bgu126

A. Carbia-nagashima, J. Gerez, C. Perez-castro, M. Paez-pereda, S. Silberstein et al., RSUME, a Small RWD-Containing Protein, Enhances SUMO Conjugation and Stabilizes HIF-1?? during Hypoxia, Cell, vol.131, issue.2, pp.309-323, 2007.
DOI : 10.1016/j.cell.2007.07.044

J. Cheng, X. Kang, S. Zhang, and E. Yeh, SUMO-Specific Protease 1 Is Essential for Stabilization of HIF1?? during Hypoxia, Cell, vol.131, issue.3, pp.584-595, 2007.
DOI : 10.1016/j.cell.2007.08.045

S. Bae, J. Jeong, J. Park, S. Kim, M. Bae et al., Sumoylation increases HIF-1?? stability and its transcriptional activity, Biochemical and Biophysical Research Communications, vol.324, issue.1, pp.394-400, 2004.
DOI : 10.1016/j.bbrc.2004.09.068

A. M. Mabb, S. M. Wuerzberger-davis, and S. Miyamoto, PIASy mediates NEMO sumoylation and NF-??B activation in response to genotoxic stress, Nature Cell Biology, vol.18, issue.9, pp.986-993, 2006.
DOI : 10.1128/MCB.24.11.4895-4908.2004

Q. Cai, S. C. Verma, P. Kumar, M. Ma, and E. Robertson, Hypoxia Inactivates the VHL Tumor Suppressor through PIASy-Mediated SUMO Modification, PLoS ONE, vol.5, issue.3, p.9720, 2010.
DOI : 10.1371/journal.pone.0009720.s005

J. Li, Y. Xu, X. Long, W. Wang, H. Jiao et al., Cbx4 Governs HIF-1?? to Potentiate Angiogenesis of Hepatocellular Carcinoma by Its SUMO E3 Ligase Activity, Cancer Cell, vol.25, issue.1, pp.118-131, 2014.
DOI : 10.1016/j.ccr.2013.12.008

X. Kang, J. Li, Y. Zou, Y. J. Zhang, H. Cao et al., PIASy stimulates HIF1?? SUMOylation and negatively regulates HIF1?? activity in response to hypoxia, Oncogene, vol.29, issue.41, pp.5568-5578, 2010.
DOI : 10.1074/jbc.R800050200

M. Wagegg, T. Gaber, F. Lohanatha, M. Hahne, C. Strehl et al., Hypoxia Promotes Osteogenesis but Suppresses Adipogenesis of Human Mesenchymal Stromal Cells in a Hypoxia-Inducible Factor-1 Dependent Manner, PLoS ONE, vol.7, issue.9, p.46483, 2012.
DOI : 10.1371/journal.pone.0046483.t005

C. Hudak, O. Gulyaeva, Y. Wang, S. Park, L. Lee et al., Pref-1 Marks Very Early Mesenchymal Precursors Required for Adipose Tissue Development and Expansion, Cell Reports, vol.8, issue.3, pp.678-687, 2014.
DOI : 10.1016/j.celrep.2014.06.060

X. Li, J. Ding, Z. Zheng, X. Li, Z. Wu et al., Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells, Mol Med Rep, vol.6, pp.1183-1189, 2012.

Y. Wang, Z. Zhang, C. Y. Zhang, Q. Xu, F. et al., Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation, Cytotherapy, vol.16, issue.4, p.950, 2013.
DOI : 10.1016/j.jcyt.2014.01.279

J. Estrada, Y. Torres, A. Benguría, A. Dopazo, E. Roche et al., Human mesenchymal stem cell-replicative senescence and oxidative stress are closely linked to aneuploidy, Cell Death and Disease, vol.33, issue.6, p.691, 2013.
DOI : 10.1038/nprot.2006.239

W. L. Grayson, F. Zhao, R. Izadpanah, B. Bunnell, and T. Ma, Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs, Journal of Cellular Physiology, vol.31, issue.2, pp.331-339, 2006.
DOI : 10.1002/jcp.20571

M. M. Olcina, I. P. Foskolou, S. Anbalagan, and J. Senra, Replication Stress and Chromatin Context Link ATM Activation to a Role in DNA Replication, Molecular Cell, vol.52, issue.5, pp.758-766, 2013.
DOI : 10.1016/j.molcel.2013.10.019

R. Bindra, S. Gibson, A. Meng, U. Westermark, M. Jasin et al., Hypoxia-Induced Down-regulation of BRCA1 Expression by E2Fs, Cancer Research, vol.65, issue.24, pp.11597-11604, 2005.
DOI : 10.1158/0008-5472.CAN-05-2119

R. S. Bindra and P. Glazer, Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia, Oncogene, vol.23, issue.14, pp.2048-2057, 2007.
DOI : 10.1038/sj.onc.1210001

P. Oliveira, J. Boura, M. Abecasis, J. Gimble, C. Da-silva et al., Impact of hypoxia and long-term cultivation on the genomic stability and mitochondrial performance of ex vivo expanded human stem/stromal cells, Stem Cell Research, vol.9, issue.3, pp.225-236, 2012.
DOI : 10.1016/j.scr.2012.07.001

E. P. Rogakou, C. Boon, C. Redon, and W. Bonner, Megabase Chromatin Domains Involved in DNA Double-Strand Breaks in Vivo, The Journal of Cell Biology, vol.6, issue.5, pp.905-916, 1999.
DOI : 10.1126/science.168.3937.1364

J. M. Ceruti, M. F. Ogara, C. Menéndez, I. Palmero, and E. Cánepa, Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways, Molecular and Cellular Biochemistry, vol.155, issue.1-2, pp.117-126, 2013.
DOI : 10.1007/s11010-013-1601-2

K. J. Cheung, D. Mitchell, P. Lin, and G. Li, The tumor suppressor candidate p33(ING1) mediates repair of UV-damaged DNA, Cancer Res, vol.61, pp.4974-4977, 2001.

P. Peña, R. Hom, T. Hung, H. Lin, A. Kuo et al., Histone H3K4me3 Binding Is Required for the DNA Repair and Apoptotic Activities of ING1 Tumor Suppressor, Journal of Molecular Biology, vol.380, issue.2, pp.303-312, 2008.
DOI : 10.1016/j.jmb.2008.04.061

D. Larrieu, D. Ythier, R. Binet, C. Brambilla, E. Brambilla et al., ING2 controls the progression of DNA replication forks to maintain genome stability, EMBO reports, vol.114, issue.10, pp.1168-1174, 2009.
DOI : 10.1002/ijc.23790

R. Wong, H. Lin, S. Khosravi, B. Piche, S. Jafarnejad et al., Tumour suppressor ING1b maintains genomic stability upon replication stress, Nucleic Acids Research, vol.39, issue.9, pp.3632-3642, 2011.
DOI : 10.1093/nar/gkq1337
URL : http://doi.org/10.1093/nar/gkq1337

M. Koshiji, K. To, S. Hammer, K. Kumamoto, A. Harris et al., HIF-1?? Induces Genetic Instability by Transcriptionally Downregulating MutS?? Expression, Molecular Cell, vol.17, issue.6, pp.793-803, 2005.
DOI : 10.1016/j.molcel.2005.02.015

F. J. Rodríguez-jiménez, V. Moreno-manzano, R. Lucas-dominguez, and J. Sánchez-puelles, Hypoxia Causes Downregulation of Mismatch Repair System and Genomic Instability in Stem Cells, Stem Cells, vol.83, issue.8, pp.2052-2062, 2008.
DOI : 10.1634/stemcells.2007-1016

Y. Hou, Z. Zhang, Q. Xu, H. Wang, Y. Xu et al., Inhibitor of growth 4 induces NF??B/p65 ubiquitin-dependent degradation, Oncogene, vol.33, issue.15, pp.1997-2003, 2013.
DOI : 10.1074/jbc.M608523200

Y. Galanty, R. Belotserkovskaya, J. Coates, S. Polo, K. Miller et al., Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks, Nature, vol.104, issue.7275, pp.935-939, 2009.
DOI : 10.1038/nature08657
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904806

L. Yu, S. Thakur, R. Leong-quong, K. Suzuki, A. Pang et al., Src Regulates the Activity of the ING1 Tumor Suppressor, PLoS ONE, vol.19, issue.4, p.60943, 2013.
DOI : 10.1371/journal.pone.0060943.s001

R. Geiss-friedlander and F. Melchior, Concepts in sumoylation: a decade on, Nature Reviews Molecular Cell Biology, vol.1773, issue.12, pp.947-956, 2007.
DOI : 10.1038/nrm2293

J. Lee, E. Jung, J. W. Hyun, and D. Park, -cAMP signaling, Journal of Cellular Biochemistry, vol.146, issue.Suppl. 3, pp.3681-3691, 2012.
DOI : 10.1002/jcb.24241
URL : https://hal.archives-ouvertes.fr/hal-00857436

J. Mathieu, Z. Zhang, A. Nelson, D. Lamba, T. Reh et al., Hypoxia induces re-entry of committed cells into pluripotency, STEM CELLS, vol.16, issue.4, pp.1737-1748, 2013.
DOI : 10.1002/stem.1446

Z. Yun, H. L. Maecker, R. S. Johnson, and A. J. Giaccia, Inhibition of PPAR??2 Gene Expression by the HIF-1-Regulated Gene DEC1/Stra13, Developmental Cell, vol.2, issue.3, pp.331-341, 2002.
DOI : 10.1016/S1534-5807(02)00131-4

S. Zhou, S. Lechpammer, J. S. Greenberger, and J. Glowacki, Hypoxia Inhibition of Adipocytogenesis in Human Bone Marrow Stromal Cells Requires Transforming Growth Factor-??/Smad3 Signaling, Journal of Biological Chemistry, vol.280, issue.24, pp.22688-22696, 2005.
DOI : 10.1074/jbc.M412953200

J. Cheng, R. Blum, C. Bowman, D. Hu, A. Shilatifard et al., A Role for H3K4 Monomethylation in Gene Repression and Partitioning of Chromatin Readers, Molecular Cell, vol.53, issue.6, pp.979-992, 2014.
DOI : 10.1016/j.molcel.2014.02.032

X. Xia and A. Kung, Preferential binding of HIF-1 to transcriptionally active loci determines cell-type specific response to hypoxia, Genome Biology, vol.10, issue.10, p.113, 2009.
DOI : 10.1186/gb-2009-10-10-r113

A. Noer, L. C. Lindeman, and P. Collas, Histone H3 Modifications Associated With Differentiation and Long-Term Culture of Mesenchymal Adipose Stem Cells, Stem Cells and Development, vol.18, issue.5, pp.725-736, 2009.
DOI : 10.1089/scd.2008.0189

Y. Kim, Q. Lin, D. Zelterman, and Z. Yun, Hypoxia-Regulated Delta-like 1 Homologue Enhances Cancer Cell Stemness and Tumorigenicity, Cancer Research, vol.69, issue.24, pp.9271-9280, 2009.
DOI : 10.1158/0008-5472.CAN-09-1605

O. Binda, C. Nassif, and P. Branton, SIRT1 negatively regulates HDAC1-dependent transcriptional repression by the RBP1 family of proteins, Oncogene, vol.983, issue.24, pp.3384-3392, 2008.
DOI : 10.1016/S1097-2765(00)80102-1

J. Lim, Y. Lee, Y. Chun, J. Chen, J. Kim et al., Sirtuin 1 Modulates Cellular Responses to Hypoxia by Deacetylating Hypoxia-Inducible Factor 1??, Molecular Cell, vol.38, issue.6, pp.864-878, 2010.
DOI : 10.1016/j.molcel.2010.05.023

P. Simic, K. Zainabadi, E. Bell, D. Sykes, B. Saez et al., SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating ??-catenin, EMBO Molecular Medicine, vol.7, issue.3, pp.430-440, 2013.
DOI : 10.1002/emmm.201201606

M. Gil-ortega, L. Garidou, C. Barreau, M. Maumus, L. Breasson et al., Native Adipose Stromal Cells Egress from Adipose Tissue In Vivo: Evidence During Lymph Node Activation, STEM CELLS, vol.25, issue.7, pp.1309-1320, 2013.
DOI : 10.1002/stem.1375
URL : https://hal.archives-ouvertes.fr/inserm-00840905