Cited2 in hematopoietic stem cell function

Current Opinion in Hematology

Volumn 20, Issue 4, 2013, Pages 301-307

  Du, Jinwei ^a   Yang, Yu Chung ^a  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cited2; Hematopoietic stem cell; HIF 1; metabolism; p53

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 1C; CYCLIN DEPENDENT KINASE INHIBITOR 2A; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HEAT SHOCK COGNATE PROTEIN 70; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; HISTONE ACETYLTRANSFERASE GCN5; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INSULIN; INTERLEUKIN 11; INTERLEUKIN 1ALPHA; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 9; MYC PROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PLATELET DERIVED GROWTH FACTOR; PROTEIN CITED2; PROTEIN P53; PYRUVATE DEHYDROGENASE; PYRUVATE DEHYDROGENASE KINASE; REACTIVE OXYGEN METABOLITE; REGULATOR PROTEIN; SMAD2 PROTEIN; SMAD3 PROTEIN; STAT5 PROTEIN; TRANSCRIPTION FACTOR FKHRL1; TRANSCRIPTION FACTOR GATA 2; UNCLASSIFIED DRUG;

ACETYLATION; AEROBIC METABOLISM; APOPTOSIS; BONE MARROW CELL; CELL AGING; CELL CYCLE ARREST; CELL FUNCTION; CELL INVASION; CELL METABOLISM; CELL RENEWAL; DNA BINDING; DNA REPAIR; EMBRYO DEVELOPMENT; ENERGY METABOLISM; FETUS LIVER; GENE DELETION; GENE OVEREXPRESSION; GLYCOLYSIS; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; HUMAN; HYPOXIA; LEUKEMOGENESIS; LIPID METABOLISM; METABOLIC REGULATION; NERVE CELL DIFFERENTIATION; NONHUMAN; OVERALL SURVIVAL; OXIDATIVE PHOSPHORYLATION; PREMATURE AGING; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW;

ANIMALS; ENERGY METABOLISM; HEMATOPOIESIS; HEMATOPOIETIC STEM CELLS; HUMANS; LIVER; MICE; REPRESSOR PROTEINS; TRANS-ACTIVATORS;

EID: 84880238160     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/MOH.0b013e3283606022     Document Type: Review

References (92)

1. Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med 2006; 354:1813-1826.
2. Kiel MJ, Yilmaz OH, Iwashita T, et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 2005; 121:1109-1121.
3. Osawa M, Hanada K, Hamada H, Nakauchi H. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 1996; 273:242-245.
4. Goodell MA, Brose K, Paradis G, et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 1996; 183:1797-1806.
5. Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 2003; 425:841-846.
6. Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003; 425:836-841.
7. Arai F, Hirao A, Ohmura M, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 2004; 118:149-161.
8. Grassinger J, Haylock DN, Williams B, et al. Phenotypically identical hemopoietic stem cells isolated from different regions of bone marrow have different biologic potential. Blood 2010; 116:3185-3196.
9. Cipolleschi MG, Dello Sbarba P, Olivotto M. The role of hypoxia in the maintenance of hematopoietic stem cells. Blood 1993; 82:2031-2037.
10. Cheng T, Rodrigues N, Shen H, et al. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 2000; 287:1804-1808.
11. Park IK, Qian D, Kiel M, et al. Bmi-1 is required for maintenance of adult selfrenewing haematopoietic stem cells. Nature 2003; 423:302-305.
12. Rebel VI, Kung AL, Tanner EA, et al. Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal. Proc Natl Acad Sci USA 2002; 99:14789-14794.
13. Hock H, Hamblen MJ, Rooke HM, et al. Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells. Nature 2004; 431:1002-1007.
14. Liu Y, Elf SE, Miyata Y, et al. p53 regulates hematopoietic stem cell quiescence. Cell Stem Cell 2009; 4:37-48.
15. Katayama Y, Battista M, Kao WM, et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 2006; 124:407-421.
16. Qian H, Buza-Vidas N, Hyland CD, et al. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell 2007; 1:671-684.
17. Walkley CR, Shea JM, Sims NA, et al. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell 2007; 129:1081-1095.
18. Kieslinger M, Hiechinger S, Dobreva G, et al. Early B cell factor 2 regulates hematopoietic stem cell homeostasis in a cell-nonautonomous manner. Cell Stem Cell 2010; 7:496-507.
19. Kobayashi H, Butler JM, O'Donnell R, et al. Angiocrine factors from Aktactivated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells. Nat Cell Biol 2010; 12:1046-1056.
20. Mendez-Ferrer S, Michurina TV, Ferraro F, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 2010; 466:829-834.
21. Fleming HE, Janzen V, Lo Celso C, et al. Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell 2008; 2:274-283.
22. Magee JA, Ikenoue T, Nakada D, et al. Temporal changes in PTEN and mTORC2 regulation of hematopoietic stem cell self-renewal and leukemia suppression. Cell Stem Cell 2012; 11:415-428. An interesting study showing that Rictor is required for HSC depletion and leukemogenesis following Phosphatase and tensin homolog (PTEN) deletion. PTEN is required in adult, but not neonatal, hematopoietic cells to maintain HSCs and to suppress leukemia by reducing mTORC2 activation.
23. Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 2012; 481:457-462. An important study demonstrating that HSCs reside in a perivascular niche in which multiple cell types express factors to promote HSC maintenance.
24. Sugimura R, He XC, Venkatraman A, et al. Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche. Cell 2012; 150:351-365.
25. Chen Y, Haviernik P, Bunting KD, Yang YC. Cited2 is required for normal hematopoiesis in the murine fetal liver. Blood 2007; 110:2889-2898.
26. Kranc KR, Schepers H, Rodrigues NP, et al. Cited2 is an essential regulator of adult hematopoietic stem cells. Cell Stem Cell 2009; 5:659-665.
27. Du J, Chen Y, Li Q, et al. HIF-1alpha deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency. Blood 2012; 119:2789-2798. The first demonstration that conditional deletion of Cited2 not only increases the apoptosis of HSCs as observed previously by an other group, but also significantly impairs the quiescence which is partially rescued by additional deletion of HIF-1a. It is consistent with the previous finding that precise regulation of HIF-1 activity is important for the maintenance of HSCs.
28. Shioda T, Fenner MH, Isselbacher KJ. msg1, a novel melanocyte-specific gene, encodes a nuclear protein and is associated with pigmentation. Proc Natl Acad Sci USA 1996; 93:12298-12303.
29. Shioda T, Fenner MH, Isselbacher KJ. MSG1 and its related protein MRG1 share a transcription activating domain. Gene 1997; 204:235-241.
30. Sun HB, Zhu YX, Yin T, et al. MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity. Proc Natl Acad Sci USA 1998; 95:13555-13560.
31. Bhattacharya S, Michels CL, Leung MK, et al. Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1. Genes Dev 1999; 13:64-75.
32. Glenn DJ, Maurer RA. MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene expression. J Biol Chem 1999; 274:36159-36167.
33. Chen CM, Bentham J, Cosgrove C, et al. Functional significance of SRJ domain mutations in CITED2. PLoS One 2012; 7:e46256.
34. Regel I, Merkl L, Friedrich T, et al. Pan-histone deacetylase inhibitor panobinostat sensitizes gastric cancer cells to anthracyclines via induction of CITED2. Gastroenterology 2012; 143:99-109. An interesting study showing that HDAC inhibitor LBH589 can overcome the resistance of mouse gastric cancer cells to anthracyclines by inducing expression of Cited2 which is responsible for the efficient repression of chemoresistance genes.
35. Bakker WJ, Harris IS, Mak TW. FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2. Mol Cell 2007; 28:941-953.
36. Kleinschmidt MA, Streubel G, Samans B, et al. The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation. Nucl Acid Res 2008; 36:3202-3213.
37. Chou YT, Hsieh CH, Chiou SH, et al. CITED2 functions as a molecular switch of cytokine-induced proliferation and quiescence. Cell Death Differ 2012; 19:2015-2028.
38. Chou YT, Yang YC. Posttranscriptional control of Cited2 by transforming growth factor beta. Regulation via Smads and Cited2 coding region. J Biol Chem 2006; 281:18451-18462.
39. Freedman SJ, Sun ZY, Kung AL, et al. Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2. Nat Struct Biol 2003; 10:504-512.
40. Lou X, Sun S, Chen W, et al. Negative feedback regulation of NF-kappaB action by CITED2 in the nucleus. J Immunol 2011; 186:539-548.
41. Wu ZZ, Sun NK, Chao CC. Knockdown of CITED2 using short-hairpin RNA sensitizes cancer cells to cisplatin through stabilization of p53 and enhancement of p53-dependent apoptosis. J Cell Physiol 2011; 226:2415-2428.
42. Bamforth SD, Braganca J, Eloranta JJ, et al. Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator. Nat Genet 2001; 29:469-474.
43. Qu X, Lam E, Doughman YQ, et al. Cited2, a coactivator of HNF4alpha, is essential for liver development. EMBO J 2007; 26:4445-4456.
44. Chou YT, Wang H, Chen Y, et al. Cited2 modulates TGF-beta-mediated upregulation of MMP9. Oncogene 2006; 25:5547-5560.
45. Tien ES, Davis JW, Vanden Heuvel JP. Identification of the CREB-binding protein/p300-interacting protein CITED2 as a peroxisome proliferatoractivated receptor alpha coregulator. J Biol Chem 2004; 279:24053- 24063.
46. Sakai M, Matsumoto M, Tujimura T, et al. CITED2 links hormonal signaling to PGC-1alpha acetylation in the regulation of gluconeogenesis. NatMed 2012; 18:612-617. An outstanding study demonstrating that Cited2 in liver cells interacts with GCN5 and thereby blocks the acetylation of PGC-1a mediated by GCN5. Decreased acetylation of PGC-1a leads to increased expression of gluconeogenic genes. More importantly, loss of Cited2 function suppresses gluconeogenesis in diabetic mice, suggesting a therapeutic potential of Cited2 in hyperglycemia.
47. Bamforth SD, Braganca J, Farthing CR, et al. Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway. Nat Genet 2004; 36:1189-1196.
48. Chen Y, Doughman YQ, Gu S, et al. Cited2 is required for the proper formation of the hyaloid vasculature and for lens morphogenesis. Development 2008; 135:2939-2948.
49. Xu B, Qu X, Gu S, et al. Cited2 is required for fetal lung maturation. Dev Biol 2008; 317:95-105.
50. Pritsker M, Ford NR, Jenq HT, Lemischka IR. Genomewide gain-of-function genetic screen identifies functionally active genes in mouse embryonic stem cells. Proc Natl Acad Sci USA 2006; 103:6946-6951.
51. Li Q, Ramirez-Bergeron DL, Dunwoodie SL, Yang YC. Cited2 controls pluripotency and cardiomyocyte differentiation of murine embryonic stem cells through Oct4. J Biol Chem 2012; 287:29088-29100. The first demonstration that loss of Cited2 in murine embryonic stem cells results in disturbance in cardiomyocyte, hematopoietic and neuronal differentiation.
52. Bai L, Merchant JL. A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion. FEBS Lett 2007; 581:5904-5910.
53. van Agthoven T, Sieuwerts AM, Veldscholte J, et al. CITED2 and NCOR2 in antioestrogen resistance and progression of breast cancer. Br J Cancer 2009; 101:1824-1832.
54. Morrison SJ, Hemmati HD, Wandycz AM, Weissman IL. The purification and characterization of fetal liver hematopoietic stem cells. Proc Natl Acad Sci USA 1995; 92:10302-10306.
55. Rebel VI, Miller CL, Eaves CJ, Lansdorp PM. The repopulation potential of fetal liver hematopoietic stem cells in mice exceeds that of their liver adult bone marrow counterparts. Blood 1996; 87:3500-3507.
56. Kranc KR, Bamforth SD, Braganca J, et al. Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF. Mol Cell Biol 2003; 23:7658-7666.
57. Blobel GA. CREB-binding protein and p300: molecular integrators of hematopoietic transcription. Blood 2000; 95:745-755.
58. Tsai FY, Keller G, Kuo FC, et al. An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 1994; 371:221-226.
59. Tsai FY, Orkin SH. Transcription factor GATA-2 is required for proliferation/ survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood 1997; 89:3636-3643.
60. Ling KW, Ottersbach K, van Hamburg JP, et al. GATA-2 plays two functionally distinct roles during the ontogeny of hematopoietic stem cells. J Exp Med 2004; 200:871-882.
61. Zhong JF, Zhao Y, Sutton S, et al.Gene expression profile of murine long-term reconstituting vs. short-term reconstituting hematopoietic stem cells. Proc Natl Acad Sci USA 2005; 102:2448-2453.
62. Dumble M, Moore L, Chambers SM, et al. The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging. Blood 2007; 109:1736-1742.
63. Abbas HA, Maccio DR, Coskun S, et al. Mdm2 is required for survival of hematopoietic stem cells/progenitors via dampening of ROS-induced p53 activity. Cell Stem Cell 2010; 7:606-617.
64. Milyavsky M, Gan OI, Trottier M, et al. A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal. Cell Stem Cell 2010; 7:186-197.
65. Takubo K, Goda N, Yamada W, et al. Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell 2010; 7:391-402.
66. Xu B, Doughman Y, Turakhia M, et al. Partial rescue of defects in Cited2- deficient embryos by HIF-1alpha heterozygosity. Dev Biol 2007; 301:130-140.
67. Huang TQ, Wang Y, Ebrahem Q, et al. Deletion of HIF-1alpha partially rescues the abnormal hyaloid vascular system in Cited2 conditional knockout mouse eyes. Mol Vis 2012; 18:1260-1270.
68. Min IM, Pietramaggiori G, Kim FS, et al. The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells. Cell Stem Cell 2008; 2:380-391.
69. Chen SJ, Ning H, Ishida W, et al. The early-immediate gene EGR-1 is induced by transforming growth factor-beta and mediates stimulation of collagen gene expression. J Biol Chem 2006; 281:21183-21197.
70. Matsumoto A, Takeishi S, Kanie T, et al. p57 is required for quiescence and maintenance of adult hematopoietic stem cells. Cell Stem Cell 2011; 9:262-271.
71. Zou P, Yoshihara H, Hosokawa K, et al. p57(Kip2) and p27(Kip1) cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc70. Cell Stem Cell 2011; 9:247-261.
72. Miyamoto K, Araki KY, Naka K, et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 2007; 1:101-112.
73. Wang Z, Li G, Tse W, Bunting KD. Conditional deletion of STAT5 in adult mouse hematopoietic stem cells causes loss of quiescence and permits efficient nonablative stem cell replacement. Blood 2009; 113:4856-4865.
74. Simsek T, Kocabas F, Zheng J, et al. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell 2010; 7:380-390.
75. Ito K, Hirao A, Arai F, et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 2004; 431:997-1002.
76. Ito K, Hirao A, Arai F, et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med 2006; 12:446-451.
77. Jang YY, Sharkis SJ. A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 2007; 110:3056-3063.
78. Chen C, Liu Y, Liu R, et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med 2008; 205:2397-2408.
79. Juntilla MM, Patil VD, Calamito M, et al. AKT1 and AKT2 maintain hematopoietic stem cell function by regulating reactive oxygen species. Blood 2010; 115:4030-4038.
80. Maryanovich M, Oberkovitz G, Niv H, et al. The ATM-BID pathway regulates quiescence and survival of haematopoietic stem cells. Nat Cell Biol 2012; 14:535-541. An interesting study showing that BID phosphorylation plays a role in protecting HSCs from irradiation, and that regulating both quiescence and survival of HSCs depends on BID's ability to regulate oxidative stress.
81. Mantel C, Messina-Graham S, Moh A, et al. Mouse hematopoietic celltargeted STAT3 deletion: stem/progenitor cell defects, mitochondrial dysfunction, ROS overproduction, and a rapid aging-like phenotype. Blood 2012; 120:2589-2599. An important study showing that STAT3 deficient HSCs display dysregulation of mitochondrial activity and increased ROS levels. The results of this study raise the possibility that lack of proper STAT3 activity in mitochondria could interfere with proper ROS regulation and therefore contribute to the progression of diseases.
82. Unnisa Z, Clark JP, Roychoudhury J, et al. Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress. Blood 2012; 120:4973-4981. An interesting work demonstrating that deletion of Meis1 leads to accumulation of ROS and loss of HSC quiescence. Meis1 limits oxidative stress by maintaining HIF-1a expression and regulating the hypoxia-response pathway.
83. Miharada K, Karlsson G, Rehn M, et al. Cripto regulates hematopoietic stem cells as a hypoxic-niche-related factor through cell surface receptor GRP78. Cell Stem Cell 2011; 9:330-344.
84. Takubo K, Nagamatsu G, Kobayashi CI, et al. Regulation of glycolysis by pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. Cell Stem Cell 2013; 12:49-61. The first demonstration that Pdk2 and Pdk4, which are highly expressed in HSCs, control the utilization of glycolysis by inhibiting mitochondrial oxidation respiration while facilitating glycolysis. This work directly shows that disturbance of metabolism affects the cell cycle of HSCs.
85. Gan B, Hu J, Jiang S, et al. Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature 2010; 468:701-704.
86. Gurumurthy S, Xie SZ, Alagesan B, et al. The Lkb1 metabolic sensor maintains haematopoietic stem cell survival. Nature 2010; 468:659-663.
87. Nakada D, Saunders TL, Morrison SJ. Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells. Nature 2010; 468:653-658.
88. Ito K, Carracedo A, Weiss D, et al. A PML-PPAR-delta pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance. Nat Med 2012; 18:1350-1358. The relationship between glycolysis and HSC function is beginning to be understood, but the contribution of lipid metabolism to HSC maintenance has never been reported. This outstanding work discovers a link between the PML-PPARd- FAO pathway and control of HSC division.
89. Gonzalez YR, Zhang Y, Behzadpoor D, et al. CITED2 signals through peroxisome proliferator-activated receptor-gamma to regulate death of cortical neurons after DNA damage. J Neurosci 2008; 28:5559-5569.
90. Sykes SM, LaneSW,Bullinger L, et al.AKT/FOXOsignaling enforces reversible differentiation blockade in myeloid leukemias. Cell 2011; 146:697-708.
91. Wang Y, Liu Y, Malek SN, Zheng P. Targeting HIF1alpha eliminates cancer stem cells in hematological malignancies. Cell Stem Cell 2011; 8:399-411.
92. Ghosh AK, Shanafelt TD, Cimmino A, et al. Aberrant regulation of pVHL levels by microRNA promotes the HIF/VEGF axis in CLL B cells. Blood 2009; 113:5568-5574.