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PLOS ONE  2013 

Canonical Wnt Signaling Promotes Early Hematopoietic Progenitor Formation and Erythroid Specification during Embryonic Stem Cell Differentiation

DOI: 10.1371/journal.pone.0081030

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Abstract:

The generation of hematopoietic stem cells (HSCs) during development is a complex process linked to morphogenic signals. Understanding this process is important for regenerative medicine applications that require in vitro production of HSC. In this study we investigated the effects of canonical Wnt/β-catenin signaling during early embryonic differentiation and hematopoietic specification using an embryonic stem cell system. Our data clearly demonstrates that following early differentiation induction, canonical Wnt signaling induces a strong mesodermal program whilst maintaining a degree of stemness potential. This involved a complex interplay between β-catenin/TCF/LEF/Brachyury/Nanog. β-catenin mediated up-regulation of TCF/LEF resulted in enhanced brachyury levels, which in-turn lead to Nanog up-regulation. During differentiation, active canonical Wnt signaling also up-regulated key transcription factors and cell specific markers essential for hematopoietic specification, in particular genes involved in establishing primitive erythropoiesis. This led to a significant increase in primitive erythroid colony formation. β-catenin signaling also augmented early hematopoietic and multipotent progenitor (MPP) formation. Following culture in a MPP specific cytokine cocktail, activation of β-catenin suppressed differentiation of the early hematopoietic progenitor population, with cells displaying a higher replating capacity and a propensity to form megakaryocytic erythroid progenitors. This bias towards erythroid lineage commitment was also observed when hematopoietic progenitors were directed to undergo myeloid colony formation. Overall this study underscores the importance of canonical Wnt/β-catenin signaling in mesodermal specification, primitive erythropoiesis and early hematopietic progenitor formation during hematopoietic induction.

References

[1]  Van Den Berg DJ, Sharma AK, Bruno E, Hoffman R (1998) Role of members of the wnt gene family in human hematopoiesis. Blood 92: 3189-3202. PubMed: 9787155.
[2]  Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D et al. (1996) Functional interaction of [beta]-catenin with the transcription factor LEF-1. Nature 382: 638-642. doi:10.1038/382638a0. PubMed: 8757136.
[3]  Huelsken J, Vogel R, Brinkmann V, Erdmann B, Birchmeier C et al. (2000) Requirement for β-catenin in anterior-posterior axis formation in mice. J Cell Biol 148: 567-578. doi:10.1083/jcb.148.3.567. PubMed: 10662781.
[4]  Ysebaert L, Chicanne G, Demur C, De Toni F, Prade-Houdellier N et al. (2006) Expression of [beta]-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis. Leukemia 20: 1211-1216. doi:10.1038/sj.leu.2404239. PubMed: 16688229.
[5]  Clements WK, Kim AD, Ong KG, Moore JC, Lawson ND et al. (2011) A somitic Wnt16/Notch pathway specifies haematopoietic stem cells. Nature 474: 220-224. doi:10.1038/nature10107. PubMed: 21654806.
[6]  de Andrés B, Gonzalo P, Minguet S, Martínez-Marin JA, Soro PG et al. (2002) The first 3 days of B-cell development in the mouse embryo. Blood 100: 4074-4081. doi:10.1182/blood-2002-03-0809. PubMed: 12393735.
[7]  Austin TW, Solar GP, Ziegler FC, Liem L, Matthews W (1997) A role for the wnt gene family in hematopoiesis: Expansion of multilineage progenitor cells. Blood 89: 3624-3635. PubMed: 9160667.
[8]  Corrigan PM, Dobbin E, Freeburn RW, Wheadon H (2009) Patterns of Wnt/Fzd/LRP gene expression during embryonic hematopoiesis. Stem Cells Dev 18: 759-772. doi:10.1089/scd.2008.0270. PubMed: 18800919.
[9]  Tran HT, Sekkali B, Van Imschoot G, Janssens S, Vleminckx K (2010) Wnt/β-catenin signaling is involved in the induction and maintenance of primitive hematopoiesis in the vertebrate embryo. Proceedings of the National Academy of Sciences of the USA 107: 16160-16165. doi:10.1073/pnas.1007725107.
[10]  Lacaud G, Robertson S, Palis J, Kennedy M, Keller G (2001) Regulation of hemangioblast development. Ann N Y Acad Sci 938: 96-108. PubMed: 11458531.
[11]  Ema H, Nakauchi H (2000) Expansion of hematopoietic stem cells in the developing liver of a mouse embryo. Blood 95: 2284-2288. PubMed: 10733497.
[12]  Takada S, Stark KL, Shea MJ, Vassileva G, McMahon JA et al. (1994) Wnt-3a regulates somite and tailbud formation in the mouse embryo. Genes Dev 8: 174-189. doi:10.1101/gad.8.2.174. PubMed: 8299937.
[13]  Luis TC, Weerkamp F, Naber BAE, Baert MRM, de Haas EFE et al. (2009) Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation. Blood 113: 546-554. doi:10.1182/blood-2008-06-163774. PubMed: 18832654.
[14]  Ruiz-Herguido C, Guiu J, D'Altri T, Inglés-Esteve J, Dzierzak E et al. (2012) Hematopoietic stem cell development requires transient wnt/β-catenin activity. J Exp Med, 209: 1457–68. PubMed: 22802352 .
[15]  Reya T, Duncan AW, Ailles L, Domen J, Scherer DC et al. (2003) A role for wnt signalling in self-renewal of haematopoietic stem cells. Nature 423: 409-414. doi:10.1038/nature01593. PubMed: 12717450.
[16]  Zhao C, Blum J, Chen A, Kwon HY, Jung SH et al. (2007) Loss of β-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell 12: 528-541. doi:10.1016/j.ccr.2007.11.003. PubMed: 18068630.
[17]  Fleming HE, Janzen V, Lo Celso C, Guo J, Leahy KM et al. (2008) Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell 2: 274-283. doi:10.1016/j.stem.2008.01.003. PubMed: 18371452.
[18]  Cobas M, Wilson A, Ernst B, Mancini SJC, MacDonald HR et al. (2004) ?-Catenin is dispensable for hematopoiesis and lymphopoiesis. J Exp Med 199: 221-229. doi:10.1084/jem.20031615. PubMed: 14718516.
[19]  Jeannet G, Scheller M, Scarpellino L, Duboux S, Gardiol N et al. (2008) Long-term, multilineage hematopoiesis occurs in the combined absence of β-catenin and γ-catenin. Blood 111: 142-149. doi:10.1182/blood-2007-07-102558. PubMed: 17906078.
[20]  Koch U, Wilson A, Cobas M, Kemler R, MacDonald HR et al. (2008) Simultaneous loss of β- and γ-catenin does not perturb hematopoiesis or lymphopoiesis. Blood 111: 160-164. doi:10.1182/blood-2007-07-099754. PubMed: 17855627.
[21]  Kirstetter P, Anderson K, Porse BT, Jacobsen SEW, Nerlov C (2006) Activation of the canonical wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nat Immunol 7: 1048-1056. doi:10.1038/ni1381. PubMed: 16951689.
[22]  Scheller M, Huelsken J, Rosenbauer F, Taketo MM, Birchmeier W et al. (2006) Hematopoietic stem cell and multilineage defects generated by constitutive [beta]-catenin activation. Nat Immunol 7: 1037-1047. doi:10.1038/ni1387. PubMed: 16951686.
[23]  Baba Y, Garrett KP, Kincade PW (2005) Constitutively active 2-catenin confers multilineage differentiation potential on lymphoid and myeloid progenitors. Immunity 23: 599-609. doi:10.1016/j.immuni.2005.10.009. PubMed: 16356858.
[24]  Malhotra S, Baba Y, Garrett KP, Staal FJT, Gerstein R et al. (2008) Contrasting responses of lymphoid progenitors to canonical and noncanonical wnt signals. Journal of Immunology 181: 3955-3964. PubMed: 18768850.
[25]  Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL et al. (2003) Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423: 448-452. doi:10.1038/nature01611. PubMed: 12717451.
[26]  Luis TC, Naber BE, Roozen PC, Brugman MH, de?Haas EE et al. (2011) Canonical wnt signaling regulates hematopoiesis in a dosage-dependent fashion. Cell Stem Cell 9: 345-356. doi:10.1016/j.stem.2011.07.017. PubMed: 21982234.
[27]  Gordon MK (1995) In vitro differentiation of embryonic stem cells. Curr Opin Cell Biol 7: 862-869. doi:10.1016/0955-0674(95)80071-9. PubMed: 8608017.
[28]  Keller G, Kennedy M, Papayannopoulou T, Wiles MV (1993) Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol 13: 473-486. PubMed: 8417345.
[29]  Wiles MV, Keller G (1991) Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development 111: 259-267. PubMed: 1893864.
[30]  Smith AG (2001) Embryo derived stem cells: Of mice and men. Annu Rev Cell Dev Biol 17: 435-462. doi:10.1146/annurev.cellbio.17.1.435. PubMed: 11687496.
[31]  Keller G, Lacaud G, Robertson S (1999) Development of the hematopoietic system in the mouse. Exp Hematol 27: 777-787. doi:10.1016/S0301-472X(99)00024-7. PubMed: 10340392.
[32]  Dzierzak E (2003) Ontogenic emergence of definitive hematopoietic stem cells. Curr Opin Hematol 10: 229-234. doi:10.1097/00062752-200305000-00006. PubMed: 12690291.
[33]  Kennedy M, D'Souza SL, Lynch-Kattman M, Schwantz S, Keller G (2007) Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures. Blood 109: 2679-2687. PubMed: 17148580.
[34]  Fehling HJ, Lacaud G, Kubo A, Kennedy M, Robertson S et al. (2003) Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation. Development 130: 4217-4227. doi:10.1242/dev.00589. PubMed: 12874139.
[35]  Nostro MC, Cheng X, Keller GM, Gadue P (2008) Wnt, activin, and BMP signaling regulate distinct stages in the developmental pathway from embryonic stem cells to blood. Cell Stem Cell 2: 60-71. doi:10.1016/j.stem.2007.10.011. PubMed: 18371422.
[36]  Cheng X, Huber TL, Chen VC, Gadue P, Keller GM (2008) Numb mediates the interaction between wnt and notch to modulate primitive erythropoietic specification from the hemangioblast. Development 135: 3447-3458. doi:10.1242/dev.025916. PubMed: 18799543.
[37]  Lengerke C, Schmitt S, Bowman TV, Jang IH, Maouche-Chretien L et al. (2008) BMP and wnt specify hematopoietic fate by activation of the cdx-hox pathway. Cell Stem Cell 2: 72-82. doi:10.1016/j.stem.2007.10.022. PubMed: 18371423.
[38]  Dobbin E, Corrigan PM, Walsh CP, Welham MJ, Freeburn RW et al. (2008) Tel/PDGFRβ inhibits self-renewal and directs myelomonocytic differentiation of ES cells. Leuk Res 32: 1554-1564. doi:10.1016/j.leukres.2008.02.007. PubMed: 18355917.
[39]  Huang C, Qin D (2010) Role of Lef1 in sustaining self-renewal in mouse embryonic stem cells. J Genet Genomics 37: 441-449. doi:10.1016/S1673-8527(09)60063-1. PubMed: 20659708.
[40]  Yuen D, Mittal L, Deng CX, Choi K (1998) Generation of a primitive erythroid cell line and promotion of its growth by basic fibroblast growth factor. Blood 91: 3202-3209. PubMed: 9558375.
[41]  Baik J, Borges L, Magli A, Thatava T, Perlingeiro RCR (2012) Effect of endoglin overexpression during embryoid body development. Exp Hematol 40: 837-846. doi:10.1016/j.exphem.2012.06.007. PubMed: 22728030.
[42]  Akashi K, Traver D, Miyamoto T, Weissman IL (2000) A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404: 193-197. doi:10.1038/35004599. PubMed: 10724173.
[43]  Barth AIM, Pollack AL, Altschuler Y, Mostov KE, Nelson WJ (1997) NH2-terminal deletion of β-catenin results in stable colocalization of mutant β-catenin with adenomatous polyposis coli protein and altered MDCK cell adhesion. J Cell Biol 136: 693-706. doi:10.1083/jcb.136.3.693. PubMed: 9024698.
[44]  Paling NRD, Wheadon H, Bone HK, Welham MJ (2004) Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling. J Biol Chem 279: 48063-48070. doi:10.1074/jbc.M406467200. PubMed: 15328362.
[45]  Arnold SJ, Stappert J, Bauer A, Kispert A, Herrmann BG et al. (2000) Brachyury is a target gene of the wnt/β-catenin signaling pathway. Mech Dev 91: 249-258. doi:10.1016/S0925-4773(99)00309-3. PubMed: 10704849.
[46]  Suzuki A, Raya á, Kawakami Y, Morita M, Matsui T et al. (2006) Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells. Proceedings of the National Academy of Sciences of the USA 103: 10294-10299. doi:10.1073/pnas.0506945103. PubMed: 16801560.
[47]  Choi K, Kennedy M, Kazarov A, Papadimitriou JC, Keller G (1998) A common precursor for hematopoietic and endothelial cells. Development 125: 725-732. PubMed: 9435292.
[48]  Singla DK, Schneider DJ, LeWinter MM, Sobel BE (2006) wnt3a but not wnt11 supports self-renewal of embryonic stem cells. Biochem Biophys Res Commun 345: 789-795. doi:10.1016/j.bbrc.2006.04.125. PubMed: 16707109.
[49]  Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH (2004) Maintenance of pluripotency in human and mouse embryonic stem cells through activation of wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 10: 55-63. doi:10.1038/nm979. PubMed: 14702635.
[50]  Takao Y, Yokota T, Koide H (2007) β-Catenin up-regulates nanog expression through interaction with oct-3/4 in embryonic stem cells. Biochem Biophys Res Commun 353: 699-705. doi:10.1016/j.bbrc.2006.12.072. PubMed: 17196549.
[51]  Russ AP, Wattler S, Colledge WH, Aparicio SAJR, Carlton MBL et al. (2000) Eomesodermin is required for mouse trophoblast development and mesoderm formation. Nature 404: 95-99. doi:10.1038/35003601. PubMed: 10716450.
[52]  Wardle FC, Papaioannou VE (2008) Teasing out T-box targets in early mesoderm. Curr Opin Genet Dev 18: 418-425. doi:10.1016/j.gde.2008.07.017. PubMed: 18778771.
[53]  Boulet AM, Moon AM, Arenkiel BR, Capecchi MR (2004) The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth. Dev Biol 273: 361-372. doi:10.1016/j.ydbio.2004.06.012. PubMed: 15328019.
[54]  Rojas A, De Val S, Heidt AB, Xu SM, Bristow J et al. (2005) Gata4 expression in lateral mesoderm is downstream of BMP4 and. Development 132: 3405-3417. doi:10.1242/dev.01913. PubMed: 15987774.
[55]  Morrisey EE, Ip HS, Lu MM, Parmacek MS (1996) GATA-6: A zinc finger transcription factor that is expressed in multiple cell lineages derived from lateral mesoderm. Dev Biol 177: 309-322. doi:10.1006/dbio.1996.0165. PubMed: 8660897.
[56]  Saijoh Y, Adachi H, Mochida K, Ohishi S, Hirao A et al. (1999) Distinct transcriptional regulatory mechanisms underlie left–right asymmetric expression of lefty-1 and lefty-2. Genes and Development 13: 259-269. doi:10.1101/gad.13.3.259.
[57]  Anton R, Kestler HA, Kühl M (2007) β-Catenin signaling contributes to stemness and regulates early differentiation in murine embryonic stem cells. FEBS Lett 581: 5247-5254. doi:10.1016/j.febslet.2007.10.012. PubMed: 17950287.
[58]  Suzuki A, Raya A, Kawakami Y, Morita M, Matsui T et al. (2006) Maintenance of embryonic stem cell pluripotency by nanog-mediated reversal of mesoderm specification. Nat Clin Pract Cardiovasc Med, 3 Suppl 1: S114–22. PubMed: 16501617.
[59]  ten Berge D, Kurek D, Blauwkamp T, Koole W, Maas A et al. (2011) Embryonic stem cells require wnt proteins to prevent differentiation to epiblast stem cells. Nat Cell Biol 13: 1070-1075. doi:10.1038/ncb2314. PubMed: 21841791.
[60]  Luis TC, Staal FJT (2009) WNT proteins: Environmental factors regulating HSC fate in the niche. Ann N Y Acad Sci 1176: 70-76. doi:10.1111/j.1749-6632.2009.04566.x. PubMed: 19796234.
[61]  Ema M, Yokomizo T, Wakamatsu A, Terunuma T, Yamamoto M et al. (2006) Primitive erythropoiesis from mesodermal precursors expressing VE-cadherin, PECAM-1, Tie2, endoglin, and CD34 in the mouse embryo. Blood 108: 4018-4024. doi:10.1182/blood-2006-03-012872. PubMed: 16926294.
[62]  Shivdasani RA, Fujiwara Y, McDevitt MA, Orkin SH (1997) A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development. EMBO J 16: 3965-3973. doi:10.1093/emboj/16.13.3965. PubMed: 9233806.
[63]  Warren AJ, Colledge WH, Carlton MBL, Evans MJ, Smith AJH et al. (1994) The oncogenic cysteine-rich LIM domain protein Rbtn2 is essential for erythroid development. Cell 78: 45-57. doi:10.1016/0092-8674(94)90571-1. PubMed: 8033210.
[64]  Yamada Y, Warren AJ, Dobson C, Forster A, Pannell R et al. (1998) The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis. Proceedings of the National Academy of Sciences of the USA 95: 3890-3895. doi:10.1073/pnas.95.7.3890.
[65]  Trompouki E, Bowman TV, Lawton LN, Fan ZP, Wu DC et al. (2011) Lineage regulators direct BMP and wnt pathways to cell-specific programs during differentiation and regeneration. Cell 147: 577-589. doi:10.1016/j.cell.2011.09.044. PubMed: 22036566.
[66]  Wadman IA, Osada H, Grütz GG, Agulnick AD, Westphal H et al. (1997) The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins. EMBO J 16: 3145-3157. doi:10.1093/emboj/16.11.3145. PubMed: 9214632.
[67]  Crispino JD, Lodish MB, MacKay JP, Orkin SH (1999) Use of altered specificity mutants to probe a specific ProteinProtein interaction in differentiation: The GATA-1:FOG complex. Mol Cell 3: 219-228. doi:10.1016/S1097-2765(00)80312-3. PubMed: 10078204.
[68]  Shimizu R, Takahashi S, Ohneda K, Engel JD, Yamamoto M (2001) In vivo requirements for GATA-1 functional domains during primitive and definitive erythropoiesis. EMBO J 20: 5250-5260. doi:10.1093/emboj/20.18.5250. PubMed: 11566888.
[69]  Kingsley PD, Malik J, Fantauzzo KA, Palis J. (2004) Yolk sac-derived primitive erythroblasts enucleate during mammalian embryogenesis. Blood 104: 19-25.
[70]  Robertson SM, Kennedy M, Shannon JM, Keller G (2000) A transitional stage in the commitment of mesoderm to hematopoiesis requiring the transcription factor SCL/tal-1. Development 127: 2447-2459. PubMed: 10804185.
[71]  Nielsen PJ, Lorenz B, Müller AM, Wenger RH, Brombacher F et al. (1997) Altered erythrocytes and a leaky block in B-cell development in CD24/HSA-deficient mice. Blood 89: 1058-1067. PubMed: 9028339.
[72]  Mikkola HKA, Orkin SH (2006) The journey of developing hematopoietic stem cells. Development 133: 3733-3744. doi:10.1242/dev.02568. PubMed: 16968814.
[73]  Tanaka TS, Kunath T, Kimber WL, Jaradat SA, Stagg CA et al. (2002) Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity. Genome Res 12: 1921-1928. doi:10.1101/gr.670002. PubMed: 12466296.
[74]  Tanaka Y, Joshi A, Wilson NK, Kinston S, Nishikawa S et al. (2012) The transcriptional programme controlled by Runx1 during early embryonic blood development. Dev Biol 366: 404-419. doi:10.1016/j.ydbio.2012.03.024. PubMed: 22554697.
[75]  Mikkola HKA, Fujiwara Y, Schlaeger TM, Traver D, Orkin SH (2003) Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo. Blood 101: 508-516. doi:10.1182/blood-2002-06-1699. PubMed: 12393529.

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