Regulatory signaling pathways in hematopoietic stem cell development
Received date: 2021-01-20
Revised date: 2021-03-01
Online published: 2021-03-15
Supported by
Supported by the National Key Research and Development Program of China Nos(2018YFA0800200);Supported by the National Key Research and Development Program of China Nos(2018YFA080100);the Strategic Priority Research Program of the Chinese Academy of Sciences, China No(XDA16010207);the National Natural Science Foundation of China (Nos)(32030032);the National Natural Science Foundation of China (Nos)(31830061)
The blood system provides the body with oxygen and nutrients, maintains the homeostasis of the internal environment through material exchange, and keeps the body with immune defense and protection. Hematopoietic stem cells (HSCs), which are pluripotent adult stem cells with self-renewal and differentiation potential, are the origin of mature blood cells in the body. The production, development and maturation processes of HSCs and their derivatives are the so-called ‘hematopoiesis’, which begins in the early embryonic development and throughout the life course; any abnormality during these processes can cause the occurrence of hematological diseases. Therefore, a deeper understanding of hematopoietic development and its regulation is important to the diagnosis and treatment of blood diseases. In recent years, a series of advances have been made in studying hematopoietic development using mice and zebrafish as animal models. It has been shown that BMP, Notch and Wnt signaling pathways play an important role in the fate determination and generation of HSCs. In this review, we systematically summarize the regulatory roles of these signaling pathways in the hematopoietic process of mice and zebrafish embryos, to improve our understanding on the underlying regulatory network of hematopoietic development and provide guidance for clinical application.
Key words： hematopoietic stem cell; signaling pathways; BMP; Notch; Wnt
Chunxia Zhang, Feng Liu . Regulatory signaling pathways in hematopoietic stem cell development[J]. Hereditas(Beijing), 2021 , 43(4) : 295 -307 . DOI: 10.16288/j.yczz.21-026
| [1] | Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell, 2008,132(4):631-644. |
| [2] | Choi K, Kennedy M, Kazarov A, Papadimitriou JC, Keller G. A common precursor for hematopoietic and endothelial cells. Development, 1998,125(4):725-732. |
| [3] | Palis J, Robertson S, Kennedy M, Wall C, Keller G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development, 1999,126(22):5073-5084. |
| [4] | Chen MJ, Li Y, De Obaldia ME, Yang Q, Yzaguirre AD, Yamada-Inagawa T, Vink CS, Bhandoola A, Dzierzak E, Speck NA. Erythroid/myeloid progenitors and hematopoietic stem cells originate from distinct populations of endothelial cells. Cell Stem Cell, 2011,9(6):541-552. |
| [5] | McGrath KE, Frame JM, Fegan KH, Bowen JR, Conway SJ, Catherman SC, Kingsley PD, Koniski AD, Palis J. Distinct sources of hematopoietic progenitors emerge before HSCs and provide functional blood cells in the mammalian embryo. Cell Rep, 2015,11(12):1892-1904. |
| [6] | Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu BS, Jacobsen SEW, Pollard JW, Frampton J, Liu KJ, Geissmann F. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science, 2012,336(6077):86-90. |
| [7] | Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E, Crozet L, Garner H, Trouillet C, de Bruijn MF, Geissmann F, Rodewald HR. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature, 2015,518(7540):547-551. |
| [8] | B?iers C, Carrelha J, Lutteropp M, Luc S, Green JCA, Azzoni E, Woll PS, Mead AJ, Hultquist A, Swiers G, Perdiguero EG, Macaulay IC, Melchiori L, Luis TC, Kharazi S, Bouriez-Jones T, Deng QL, Ponten A, Atkinson D, Jensen CT, Sitnicka E, Geissmann F, Godin I, Sandberg R, de Bruijn MFTR, Jacobsen SEW. Lymphomyeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells. Cell Stem Cell, 2013,13(5):535-548. |
| [9] | Müller AM, Medvinsky A, Strouboulis J, Grosveld F, Dzierzak E. Development of hematopoietic stem cell activity in the mouse embryo. Immunity, 1994,1(4):291-301. |
| [10] | Gekas C, Dieterlen-Lievre F, Orkin SH, Mikkola HKA. The placenta is a niche for hematopoietic stem cells. Dev Cell, 2005,8(3):365-375. |
| [11] | Boisset JC, van Cappellen W, Andrieu-Soler C, Galjart N, Dzierzak E, Robin C. In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium. Nature, 2010,464(7285):116-120. |
| [12] | Chen AT, Zon LI. Zebrafish blood stem cells. J Cell Biochem, 2009,108(1):35-42. |
| [13] | Detrich HW, Kieran MW, Chan FY, Barone LM, Yee K, Rundstadler JA, Pratt S, Ransom D, Zon LI. Intraembryonic hematopoietic cell migration during vertebrate development. Proc Natl Acad Sci USA, 1995,92(23):10713-10717. |
| [14] | Bertrand JY, Kim AD, Violette EP, Stachura DL, Cisson JL, Traver D. Definitive hematopoiesis initiates through a committed erythromyeloid progenitor in the zebrafish embryo. Development, 2007,134(23):4147-4156. |
| [15] | Kissa K, Herbomel P. Blood stem cells emerge from aortic endothelium by a novel type of cell transition. Nature, 2010,464(7285):112-115. |
| [16] | Patterson LJ, Gering M, Patient R. Scl is required for dorsal aorta as well as blood formation in zebrafish embryos. Blood, 2005,105(9):3502-3511. |
| [17] | Ren X, Gomez GA, Zhang B, Lin S. Scl isoforms act downstream of etsrp to specify angioblasts and definitive hematopoietic stem cells. Blood, 2010,115(26):5338-5346. |
| [18] | Zhen FH, Lan YH, Yan B, Zhang WQ, Wen ZL. Hemogenic endothelium specification and hematopoietic stem cell maintenance employ distinct Scl isoforms. Development, 2013,140(19):3977-3985. |
| [19] | North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, Weber GJ, Bowman TV, Jang IH, Grosser T, Fitzgerald GA, Daley GQ, Orkin SH, Zon LI. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature, 2007,447(7147):1007-1011. |
| [20] | Wang Q, Stacy T, Binder M, Marin-Padilla M, Sharpe AH, Speck NA. Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc Natl Acad Sci USA, 1996,93(8):3444-3449. |
| [21] | Chen MJ, Yokomizo T, Zeigler BM, Dzierzak E, Speck NA. Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature, 2009,457(7231):887-891. |
| [22] | Lancrin C, Mazan M, Stefanska M, Patel R, Lichtinger M, Costa G, Vargel O, Wilson NK, M?r?y T, Bonifer C, G?ttgens B, Kouskoff V, Lacaud G. GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment. Blood, 2012,120(2):314-322. |
| [23] | Eich C, Arlt J, Vink CS, Solaimani Kartalaei P, Kaimakis P, Mariani SA, van der Linden R, van Cappellen WA, Dzierzak E. In vivo single cell analysis reveals Gata2 dynamics in cells transitioning to hematopoietic fate. J Exp Med, 2018,215(1):233-248. |
| [24] | de Pater E, Kaimakis P, Vink CS, Yokomizo T, Yamada-Inagawa T, van der Linden R, Kartalaei PS, Camper SA, Speck N, Dzierzak E. Gata2 is required for HSC generation and survival. J Exp Med, 2013,210(13):2843-2850. |
| [25] | Gao X, Johnson KD, Chang YI, Boyer ME, Dewey CN, Zhang J, Bresnick EH. Gata2 cis-element is required for hematopoietic stem cell generation in the mammalian embryo. J Exp Med, 2013,210(13):2833-2842. |
| [26] | Patterson LJ, Gering M, Eckfeldt CE, Green AR, Verfaillie CM, Ekker SC, Patient R. The transcription factors Scl and Lmo2 act together during development of the hemangioblast in zebrafish. Blood, 2006,109(6):2389-2398. |
| [27] | Butko E, Distel M, Pouget C, Weijts B, Kobayashi I, Ng K, Mosimann C, Poulain FE, McPherson A, Ni CW, Stachura DL, Del Cid N, Espín-Palazón R, Lawson ND, Dorsky R, Clements WK, Traver D. Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo. Development, 2015,142(6):1050-1061. |
| [28] | Dobrzycki T, Mahony CB, Krecsmarik M, Koyunlar C, Rispoli R, Peulen-Zink J, Gussinklo K, Fedlaoui B, de Pater E, Patient R, Monteiro R. Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult Zebrafish haematopoiesis. Commun Biol, 2020,3(1):71. |
| [29] | Massagué J. TGF-β SIGNAL TRANSDUCTION. Annu Rev Biochem, 1998,67(1):753-791. |
| [30] | Wang RN, Green J, Wang ZL, Deng YL, Qiao M, Peabody M, Zhang Q, Ye JX, Yan ZJ, Denduluri S, Idowu O, Li M, Shen C, Hu A, Haydon RC, Kang R, Mok J, Lee MJ, Luu HL, Shi LL. Bone Morphogenetic Protein(BMP) signaling in development and human diseases. Genes Dis, 2014,1(1):87-105. |
| [31] | Massagué J, Seoane J, Wotton D. Smad transcription factors. Genes Dev, 2005,19(23):2783-2810. |
| [32] | Hata A, Seoane J, Lagna G, Montalvo E, Hemmati- Brivanlou A, Massagué J. OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways. Cell, 2000,100(2):229-240. |
| [33] | Kim DW, Lassar AB. Smad-dependent recruitment of a histone deacetylase/Sin3A complex modulates the bone morphogenetic protein-dependent transcriptional repressor activity of Nkx3.2. Mol Cell Biol, 2003,23(23):8704-8717. |
| [34] | Hata A, Lagna G, Massagué J, Hemmati-Brivanlou A. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev, 1998,12(2):186-197. |
| [35] | Nakao A, Afrakhte M, Morén A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE , Heldin CH, ten Dijke P. Identification of Smad7, a TGFbeta- inducible antagonist of TGF-beta signalling. Nature, 1997,389(6651):631-635. |
| [36] | Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, Thomsen GH, Wrana JL. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell, 2000,6(6):1365-1375. |
| [37] | Sadlon TJ, Lewis ID, D'Andrea RJ. BMP4: its role in development of the hematopoietic system and potential as a hematopoietic growth factor. Stem Cells, 2004,22(4):457-474. |
| [38] | Pyati UJ, Webb AE, Kimelman D. Transgenic zebrafish reveal stage-specific roles for Bmp signaling in ventral and posterior mesoderm development. Development, 2005,132(10):2333-2343. |
| [39] | Gupta S, Zhu H, Zon LI, Evans T. BMP signaling restricts hemato-vascular development from lateral mesoderm during somitogenesis. Development, 2006,133(11):2177-2187. |
| [40] | Wilkinson RN, Pouget C, Gering M, Russell AJ, Davies SG, Kimelman D, Patient R. Hedgehog and Bmp polarize hematopoietic stem cell emergence in the zebrafish dorsal aorta. Dev Cell, 2009,16(6):909-916. |
| [41] | Monteiro R, van Dinther M, Bakkers J, Wilkinson R, Patient R, ten Dijke P, Mummery C. Two novel type II receptors mediate BMP signalling and are required to establish left-right asymmetry in zebrafish. Dev Biol, 2008,315(1):55-71. |
| [42] | Durand C, Robin C, Bollerot K, Baron MH, Ottersbach K, Dzierzak E. Embryonic stromal clones reveal developmental regulators of definitive hematopoietic stem cells. Proc Natl Acad Sci USA, 2007,104(52):20838-20843. |
| [43] | McReynolds LJ, Gupta S, Figueroa ME, Mullins MC, Evans T. Smad1 and Smad5 differentially regulate embryonic hematopoiesis. Blood, 2007,110(12):3881-3890. |
| [44] | Zhang CX, Lv JH, He QP, Wang SF, Gao Y, Meng AM, Yang X, Liu F. Inhibition of endothelial ERK signalling by Smad1/5 is essential for haematopoietic stem cell emergence. Nat Commun, 2014,5:3431. |
| [45] | Cook BD, Liu S, Evans T. Smad1 signaling restricts hematopoietic potential after promoting hemangioblast commitment. Blood, 2011,117(24):6489-6497. |
| [46] | Lan Y, He WY, Li Z, Wang Y, Wang J, Gao J, Wang WL, Cheng T, Liu B, Yang X. Endothelial Smad4 restrains the transition to hematopoietic progenitors via suppression of ERK activation. Blood, 2014,123(14):2161-2171. |
| [47] | Pimanda JE, Donaldson IJ, de Bruijn MFTR, Kinston S, Knezevic K, Huckle L, Piltz S, Landry JR, Green AR, Tannahill D, G?ttgens B. The SCL transcriptional network and BMP signaling pathway interact to regulate RUNX1 activity. Proc Natl Acad Sci USA, 2007,104(3):840-845. |
| [48] | Xu RH, Ault KT, Kim J, Park MJ, Hwang YS, Peng Y, Sredni D, Kung HF. Opposite effects of FGF and BMP-4 on embryonic blood formation: roles of PV.1 and GATA-2. Dev Biol, 1999,208(2):352-361. |
| [49] | Pera EM, Ikeda A, Eivers E, De Robertis EM. Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. Genes Dev, 2003,17(24):3023-3028. |
| [50] | Yu PZ, Pan G, Yu J, Thomson JA. FGF2 sustains NANOG and switches the outcome of BMP4-induced human embryonic stem cell differentiation. Cell Stem Cell, 2011,8(3):326-334. |
| [51] | Kopan R, Ilagan MXG. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell, 2009,137(2):216-233. |
| [52] | Shawber CJ, Kitajewski J. Notch function in the vasculature: insights from zebrafish, mouse and man. Bioessays, 2004,26(3):225-234. |
| [53] | Lomeli H, Castillo-Castellanos F. Notch signaling and the emergence of hematopoietic stem cells. Dev Dyn, 2020,249(11):1302-1317. |
| [54] | Butko E, Pouget C, Traver D. Complex regulation of HSC emergence by the Notch signaling pathway. Dev Biol, 2016,409(1):129-138. |
| [55] | Lawson ND, Scheer N, Pham VN, Kim CH, Chitnis AB, Campos-Ortega JA, Weinstein BM. Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development, 2001,128(19):3675-3683. |
| [56] | Kumano K, Chiba S, Kunisato A, Sata M, Saito T, Nakagami-Yamaguchi E, Yamaguchi T, Masuda S, Shimizu K, Takahashi T, Ogawa S, Hamada Y, Hirai H. Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells. Immunity, 2003,18(5):699-711. |
| [57] | Grego-Bessa J, Luna-Zurita L, del Monte G, Bolós V, Melgar P, Arandilla A, Garratt AN, Zang H, Mukouyama YS, Chen HY, Shou WN, Ballestar E, Esteller M, Rojas A, Pérez-Pomares JM, de la Pompa JL. Notch signaling is essential for ventricular chamber development. Dev Cell, 2007,12(3):415-429. |
| [58] | Burns CE, Traver D, Mayhall E, Shepard JL, Zon LI. Hematopoietic stem cell fate is established by the Notch- Runx pathway. Genes Dev, 2005,19(19):2331-2342. |
| [59] | Robert-Moreno A, Guiu J, Ruiz-Herguido C, López ME, Inglés-Esteve J, Riera L, Tipping A, Enver T, Dzierzak E, Gridley T, Espinosa L, Bigas A. Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1. EMBO J, 2008,27(13):1886-1895. |
| [60] | Robert-Moreno A, Espinosa L, de la Pompa JL, Bigas A. RBPjkappa-dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic cells. Development, 2005,132(5):1117-1126. |
| [61] | Guiu J, Bergen DJM, De Pater E, Islam ABMMK, Ayllón V, Gama-Norton L, Ruiz-Herguido C, González J, López-Bigas N, Menendez P, Dzierzak E, Espinosa L, Bigas A. Identification of Cdca7 as a novel Notch transcriptional target involved in hematopoietic stem cell emergence. J Exp Med, 2014,211(12):2411-2423. |
| [62] | Gama-Norton L, Ferrando E, Ruiz-Herguido C, Liu ZY, Guiu J, Islam ABMMK, Lee SU, Yan MH, Guidos CJ, López-Bigas N, Maeda T, Espinosa L, Kopan R, Bigas A. Notch signal strength controls cell fate in the haemogenic endothelium. Nat Commun, 2015,6:8510. |
| [63] | Zhang PP, He QP, Chen DB, Liu WX, Wang L, Zhang CX, Ma DY, Li W, Liu B, Liu F. G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition. Cell Res, 2015,25(10):1093-1107. |
| [64] | Richard C, Drevon C, Canto PY, Villain G, Bollérot K, Lempereur A, Teillet MA, Vincent C, Rosselló Castillo C, Torres M, Piwarzyk E, Speck NA, Souyri M, Jaffredo T. Endothelio-mesenchymal interaction controls runx1 expression and modulates the notch pathway to initiate aortic hematopoiesis. Dev Cell, 2013,24(6):600-611. |
| [65] | Swift MR, Weinstein BM. Arterial-venous specification during development. Circ Res, 2009,104(5):576-588. |
| [66] | He QP, Zhang CX, Wang L, Zhang PP, Ma DY, Lv JH, Liu F. Inflammatory signaling regulates hematopoietic stem and progenitor cell emergence in vertebrates. Blood, 2015,125(7):1098-1106. |
| [67] | Espín-Palazón R, Stachura DL, Campbell CA, García- Moreno D, Del Cid N, Kim AD, Candel S, Meseguer J, Mulero V, Traver D. Proinflammatory signaling regulates hematopoietic stem cell emergence. Cell, 2014,159(5):1070-1085. |
| [68] | Liu ZB, Tu HQ, Kang YS, Xue YY, Ma DY, Zhao CT, Li HY, Wang L, Liu F. Primary cilia regulate hematopoietic stem and progenitor cell specification through Notch signaling in zebrafish. Nat Commun, 2019,10(1):1839. |
| [69] | Wei YL, Ma DY, Gao Y, Zhang CX, Wang L, Liu F. Ncor2 is required for hematopoietic stem cell emergence by inhibiting Fos signaling in zebrafish. Blood, 2014,124(10):1578-1585. |
| [70] | Zhang CX, Chen YS, Sun BF, Wang L, Yang Y, Ma DY, Lv JH, Heng J, Ding YY, Xue YY, Lu XY, Xiao W, Yang YG, Liu F. m(6)A modulates haematopoietic stem and progenitor cell specification. Nature, 2017,549(7671):273-276. |
| [71] | Heng J, Lv P, Zhang YF, Cheng XJ, Wang L, Ma DY, Liu F. Rab5c-mediated endocytic trafficking regulates hematopoietic stem and progenitor cell development via Notch and AKT signaling. PLoS Biol, 2020,18(4):e3000696. |
| [72] | Steinhart Z, Angers S. Wnt signaling in development and tissue homeostasis. Development, 2018,145(11). |
| [73] | Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell, 2012,149(6):1192-1205. |
| [74] | Daulat AM, Borg JP. Wnt/Planar cell polarity signaling: new opportunities for cancer treatment. Trends Cancer, 2017,3(2):113-125. |
| [75] | De A. Wnt/Ca 2+ signaling pathway: a brief overview . Acta Biochim Biophys Sin (Shanghai), 2011,43(10):745-756. |
| [76] | Kohn AD, Moon RT. Wnt and calcium signaling: beta-catenin-independent pathways. Cell Calcium, 2005,38(3-4):439-446. |
| [77] | Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT, Zon LI. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell, 2009,136(6):1136-1147. |
| [78] | Lengerke C, Schmitt S, Bowman TV, Jang IH, Maouche-Chretien L, McKinney-Freeman S, Davidson AJ, Hammerschmidt M, Rentzsch F, Green JBA, Zon LI, Daley GQ. BMP and Wnt specify hematopoietic fate by activation of the Cdx-Hox pathway. Cell Stem Cell, 2008,2(1):72-82. |
| [79] | Ruiz-Herguido C, Guiu J, D'Altri T, Inglés-Esteve J, Dzierzak E, Espinosa L, Bigas A. Hematopoietic stem cell development requires transient Wnt/β-catenin activity. J Exp Med, 2012,209(8):1457-1468. |
| [80] | Chanda B, Ditadi A, Iscove NN, Keller G. Retinoic acid signaling is essential for embryonic hematopoietic stem cell development. Cell, 2013,155(1):215-227. |
| [81] | Clements WK, Kim AD, Ong KG, Moore JC, Lawson ND, Traver D. A somitic Wnt16/Notch pathway specifies haematopoietic stem cells. Nature, 2011,474(7350):220-224. |
| [82] | Kim AD, Melick CH, Clements WK, Stachura DL, Distel M, Panákova D, MacRae C, Mork LA, Crump JG, Traver D. Discrete Notch signaling requirements in the specification of hematopoietic stem cells. EMBO J, 2014,33(20):2363-2373. |
| [83] | Lee Y, Manegold JE, Kim AD, Pouget C, Stachura DL, Clements WK, Traver D. FGF signalling specifies haematopoietic stem cells through its regulation of somitic Notch signalling. Nat Commun, 2014,5:5583. |
| [84] | Genthe JR, Clements WK. R-spondin 1 is required for specification of hematopoietic stem cells through Wnt16 and Vegfa signaling pathways. Development, 2017,144(4):590-600. |
/
| 〈 |
|
〉 |
www.chinagene.cn
备案号：京ICP备09063187号
