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TGF-β signaling and its role in the regulation of hematopoietic stem cells

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Systems and Synthetic Biology

Abstract

Transforming growth factor-betas (TGF-βs) and their family members that include bone morphogenic proteins and activins have been implicated in the regulation of proliferation, hibernation, quiescence and differentiation of hematopoietic stem cells (HSCs). Increasing evidence suggests that the superfamily of TGF-βs play an integral role in the intercellular cross-talk between the stem cells and their microenvironment as well as within the cells at an intracellular level. Active sites of hematopoiesis, such as fetal liver and bone marrow are known to have abundant presence of TGF-β indicating their importance in the maintenance and regulation of hematopoiesis. One of the striking features of TGF-β superfamily is the variety of effects they evoke, contingent on the developing history of the responding cells. In the present review, we discuss the Smad-dependent and Smad-independent TGF-β signaling pathways in order to understand and underscore their role in the regulation of HSCs.

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References

  • Akiyoshi S, Inoue H, Hanain JI et al (1999) c-Ski acts as a transcriptional co-repressor in transforming growth factor-β signaling through interaction with Smads. J BiolChem 274(49):35269–35277

    CAS  Google Scholar 

  • Annes JP, Munger JS, Rifkin DB (2003) Making sense of latent TGFβ activation. J Cell Sci 116:217–224

    Article  CAS  PubMed  Google Scholar 

  • Aubin J, Davy A, Soriano P (2004) In vivo convergence of BMP and MAPK signaling pathways: impact of differential Smad1 phosphorylation on development and homeostasis. Genes Dev 18:1482–1494

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Batard P, Monier MN, Fortunel N et al (2000) TGF-(beta)1 maintains hematopoietic immaturity by a reversible negative control of cell cycle and induces CD34 antigen up-modulation. J Cell Sci 113(Pt 3):383–390

    CAS  PubMed  Google Scholar 

  • Blank U, Karlsson G, Moody JL et al (2006) Smad7 promotes self-renewal of hematopoietic stem cells. Blood 108(13):4246–4254

    Article  CAS  PubMed  Google Scholar 

  • Border WA, Noble NA (1995) Targeting TGF-β for treatment of disease. Nat Med 1:1000–1001

    Article  CAS  PubMed  Google Scholar 

  • Bourdeau A, Dumont DJ, Letarte M (1999) A murine model of hereditary hemorrhagic telangiectasia. J Clin Invest 104:1343–1351

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cashman JD, Eaves AC, Raines EW et al (1990) Mechansims that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. I. Stimulatory role of a variety of cell activators and inhibitory role of TGF β1. Blood 75:96–101

    CAS  PubMed  Google Scholar 

  • Chabanon A, Desterke C, Rodenburger E et al (2008) A cross-talk between SDF-1 and TGF-β controls the quiescence/cycling switch of CD34+ progenitors through FoXO3 and mTOR. Stem Cells 26(12):3150–3161

    Article  CAS  PubMed  Google Scholar 

  • Chacko BM, Qin BY, Tiwari A et al (2004) Structural basis of heteromericSmad protein assembly in TGF-β signaling. Mol Cell 5:813–823

    Article  Google Scholar 

  • Chadwick K, Shojaei F, Gallacher L et al (2005) Smad7 alters cell fate decisions of human hematopoietic repopulating cells. Blood 105(5):1905–1915

    Article  CAS  PubMed  Google Scholar 

  • Challen GA, Boles NC, Chambers SM et al (2010) Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-β1. Cell Stem Cell 6:265–278

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cheifetz S, Bellon T, Cales C et al (1992) Endoglin is a component of the transforming growth factor-β receptor system in human endothelial cells. J Biol Chem 267:19027–19030

  • Dai JL, Schutte M, Bansal RK et al (1999) Transforming growth factor-β responsiveness in DPC4/SMAD4-null cancer cells. Mol Carcinog 26:37–43

    Article  CAS  PubMed  Google Scholar 

  • Dallas SL, Rosser JL, Mundy GR, et al (2002) Proteolysis of latent transforming growth factor-β (TGF-β)-binding protein-1 by osteoclasts. A cellular mechanism for release of TGF-β from bone matrix. J Biol Chem 277:21352–21360

  • Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425(6958):577–584

    Article  CAS  PubMed  Google Scholar 

  • Derynck R, Akhurst R, Balmain A (2001) TGF-β signaling in tumor suppression and cancer progression. Nat Gen 29:117–129

    Article  CAS  Google Scholar 

  • Di Guglielmo GM, Le Roy C, Goodfellow AF et al (2003) Distinct endocytic pathways regulate TGF-β receptor signaling and turnover. Nat Cell Biol 5:410–421

    Article  PubMed  Google Scholar 

  • Dybedal I, Guan F, Borge OJ et al (1997) Transforming growth factor-beta1 abrogates Fas induced growth suppression and apoptosis of murine bone marrow progenitor cells. Blood 90(9):3395–3403

    CAS  PubMed  Google Scholar 

  • Eaves CJ, Cahsmna JD, Kay RJ et al (1991) Mechansims that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. II. Analysis of positive and negative regulators produced by stromal cells within the adherent layer. Blood 78:110–117

    CAS  PubMed  Google Scholar 

  • Engel ME, McDonnell MA, Law BK et al (1999) Interdependent SMAD and JNK signaling in transforming growth factor-β-mediated transcription. J Biol Chem 274:37413–37420

  • Fortunel N, Hatzfeld J, Aoustin L et al (2000) Specific dose-response effects of TGF-beta1 on developmentally distinct hematopoietic stem/progenitor cells from human umbilical cord blood. Hematol J 1:126–135

    Article  CAS  PubMed  Google Scholar 

  • Fukuda K, Kawata S, Tamura S et al (1998) Transforming growth factor-β1-induced degradation of activated Src tyrosine kinase in rat fibroblasts. Oncogene 16:3349–3356

    Article  CAS  PubMed  Google Scholar 

  • Garbe A, Spyridonidis A, Mobest D et al (1997) Transforming growth factor beta 1 delays formation of granulocyte macrophage colony-forming cells, but spares more primitive progenitors during ex vivo expansion of CD34+ hematopoietic progenitor cells. Br J Hematol 99:951–958

    Article  CAS  Google Scholar 

  • Ghahary A, Tredget EE, Mi L et al (1999) Cellular responses to latent TGF-β1 is facilitated by insulin-like growth factor-II/mannose-6-phosphate receptors on MS-9 cells. Exp Cell Res 251:111–120

    Article  CAS  PubMed  Google Scholar 

  • Godár S, Hořejši V, Weidle UH et al (1999) M6P/IGFII-receptor complexes urokinase receptor and plasminogen for activation of transforming growth factor-β1. Eur J Immunol 29:1004–1013

    Article  PubMed  Google Scholar 

  • Han J, Hajjar DP, Tauras JM et al (2000) Transforming growth factor-β1 (TGF-β1) and TGF-β2 decrease expression of CD36, the type B scavenger receptor, through mitogen-activated protein kinase phosphorylation of peroxisome proliferators-activated receptor-γ. J BiolChem 275(2):1241–1246

    CAS  Google Scholar 

  • He W, Dorn DC, Erdjument-Bromage H et al (2006) Hematopoiesis controlled by distinct TIF1γ and Smad4 branches of the TGFβ pathway. Cell 125:929–941

    Article  CAS  PubMed  Google Scholar 

  • Heldin CH, Miyazono K, ten Dijke P (1997) TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 390(6659):465–471

    Article  CAS  PubMed  Google Scholar 

  • Hocevar BA, Brown TL, Howe PH (1999) TGF-β induces fibronectin synthesis through a c- Jun N-terminal kinase-dependent, Smad4-independent pathway. EMBO J 18:1345–1356

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Howe JR, Roth S, Ringold JC et al (1998) Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280:1086–1088

    Article  CAS  PubMed  Google Scholar 

  • Hu X, Zuckerman KS (2001) Transforming growth factor: signal transduction pathways, cell cycle mediation, and effects on hematopoiesis. J Hematother Stem Cell Res 10:67–74

    Article  CAS  PubMed  Google Scholar 

  • Ignotz RA and Massague J (1986) Transforming growth factor-β stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 261:4337–4345

  • Inman GJ and Hill CS (2002) Stoichiometry of active Smad-transcription factor complexes on DNA. J Biol Chem 277:51008–51116

  • Jacobsen SE, Keller JR, Ruscetti FW et al (1991) Bidirectional effects of transforming growth factor beta (TGF-beta) on colony-stimulating factor-induced human myelopoiesisin vitro: differential effects of distinct TGF-beta isoforms. Blood 78(9):2239–2247

    CAS  PubMed  Google Scholar 

  • Jacobsen FW, Stokke T, Jacobsen SE (1995) Transforming growth factor-beta potently inhibits the viability-promoting activity of stem cell factor and other cytokines and induces apoptosis of primitive murine hematopoietic progenitor cells. Blood 86(8):2957–2966

    CAS  PubMed  Google Scholar 

  • Janssens K, ten Dijke P, Janssens S et al (2005) Transforming growth factor-β1 to the bone. Endocr Rev 26(6):743–774

    Article  CAS  PubMed  Google Scholar 

  • Johnson GL, Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298:1911–1912

    Article  CAS  PubMed  Google Scholar 

  • Kale VP (2004) Differential activation of MAPK signaling pathways by TGFβ1 forms the molecular mechanism behind its dose dependent bi-directional effects on hematopoiesis. Stem Cells Dev 13:27–38

    Article  CAS  PubMed  Google Scholar 

  • Kale VP, Limaye LS (1999) Stimulation of adult human bone marrow by factors secreted by fetal liver hematopoietic cells: in vitro evaluation using semisolid clonal assay system. Stem Cells 17(2):107–116

    Article  CAS  PubMed  Google Scholar 

  • Kale VP, Vaidya AA (2004) Molecular mechanisms behind the dose-dependent differential activation of MAPK pathways induced by transforming growth factor-β1 in hematopoietic cells. Stem Cells Dev 13:536–547

    Article  CAS  PubMed  Google Scholar 

  • Karlsson G, Blank U, Moody JL et al (2007) Smad4 is critical for self-renewal of hematopoietic stem cells. J Exp Med 204(3):467–474

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Keller JR, Mantel C, Sing GK et al (1988) Transforming growth factor beta 1 selectively regulates early murine hematopoietic progenitors and inhibits the growth of IL-3-dependent myeloid leukemia cell lines. J Exp Med 168(2):737–750

    Article  CAS  PubMed  Google Scholar 

  • Keller JR, McNiece IK, Sill KT et al (1990) Transforming growth factor beta directly regulates primitive murine hematopoietic cell proliferation. Blood 75(3):596–602

    CAS  PubMed  Google Scholar 

  • Kim SJ, Letterio J (2003) Transforming growth factor-beta signaling in normal and malignant hematopoiesis. Leukemia 17:1731–1737

    Article  CAS  PubMed  Google Scholar 

  • Kishimoto K, Matsumoto K, Ninomiya-Tsuji J (2000) TAK1 mitogen-activated protein kinase kinasekinase is activated by autophosphorylation within its activation loop. J Biol Chem 275(10):7359–7364

    Article  CAS  PubMed  Google Scholar 

  • Kretzschmar M, Massague J (1998) SMADs: mediators and regulators of TGF-beta signaling. Curr Opin Genet Dev 8:103–111

    Article  CAS  PubMed  Google Scholar 

  • Larsson J, Karlsson S (2005) The role of Smad signaling in hematopoiesis. Oncogene 24:5676–5692

    Article  CAS  PubMed  Google Scholar 

  • Larsson J, Goumans MJ, Sjostrand LJ et al (2001) Abnormal angiogenesis but intact hematopoietic potential in TGF-β type I receptor-deficient mice. EMBO J 20:1663–1673

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Letterio JJ (2005) TGF-β signaling in T cells: roles in lymphoid and epithelial neoplasia. Oncogene 24:5701–5712

    Article  CAS  PubMed  Google Scholar 

  • Liberati NT, Datto MB, Frederick JP et al (1999) Smads bind directly to the Jun family of AP-1 transcription factors. PNAS 96:4844–4849

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lopez-Casillas F, Wrana JL, Massague J (1993) Betaglycan presents ligand to the TGF β signaling receptor. Cell 73:1435–1444

    Article  CAS  PubMed  Google Scholar 

  • Lu G, Kang YJ, Han J et al (2006) TAB-1 modulates intracellular localization of p38 MAP kinase and downstream signaling. J Biol Chem 281(9):6087–6095

    Article  CAS  PubMed  Google Scholar 

  • Massague J (1998) TGF-β signal transduction. Annu Rev Biochem 67:753–791

    Article  CAS  PubMed  Google Scholar 

  • McAllister KA, Grogg KM, Johnson DW et al (1994) Endoglin, a TGF-β binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 8:345–351

    Article  CAS  PubMed  Google Scholar 

  • Mishra L, Derynck R, Mishra B (2005) Transforming growth factor–β signaling in stem cells and cancer. Science 310:68–71

    Article  CAS  PubMed  Google Scholar 

  • Mulder KM (2000) Role of Ras and Mapks in TGFβ signaling. Cytokine Growth Factor Rev 11:23–35

    Article  CAS  PubMed  Google Scholar 

  • Nakao A, Afrakhte M, Moren A et al (1997) Identification of Smad7, a TGF beta-inducible antagonist of TGF-beta signalling. Nature 389(6651):631–635

    Article  CAS  PubMed  Google Scholar 

  • Ohta M, Greenberger JS, Anklesaria P et al (1987) Two forms of transforming growth factor-beta distinguished by multipotentialhaematopoietic progenitor cells. Nature 329(6139):539–541

    Article  CAS  PubMed  Google Scholar 

  • Ottmann OG, Pelus LM (1988) Differential proliferative effects of transforming growth factor betaon human hematopoietic progenitor cells. J Immunol 140(8):2661–2665

    CAS  PubMed  Google Scholar 

  • Park SM, Deering RP, Lu Y et al (2014) Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs. J Exp Med 211(1):71–87

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pierelli L, Marone M, Bonanno G et al (2002) Transforming growth factor-beta 1 causes transcriptional activation of CD34 and preserves haematopoietic stem/progenitor cell activity. Br J Haematol 118:627–637

    Article  CAS  PubMed  Google Scholar 

  • Qin BY, Lam SS, Correia JJ et al (2002) Smad3 allostery links TGF-β receptor kinase activation to transcriptional control. Genes Dev 16:1950–1963

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Quéré R, Saint-Paul L, Carmignac V et al (2014) Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells. PNAS 111(29):10592–10597

    Article  PubMed Central  PubMed  Google Scholar 

  • RafteryL A, Twombly V, Wharton K et al (1995) Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila. Genetics 139:241–254

    Google Scholar 

  • Ruscetti FW, Bartelmetz SH (2001) Transforming growth factor beta, pleiotropic regulator of hematopoietic stem cells: potential physiological and clinical relevance. Int J Hematol 74:18–25

    Article  CAS  PubMed  Google Scholar 

  • Sanford LP, Ormsby I, Gittenberger-de Groot AC et al (1997) TGFβ2 knockout mice have multiple developmental defects that are nonoverlapping with other TGFβ knockout phenotypes. Development 124:2659–2670

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sankar S, Mahooti-Brooks N, Centrella M et al (1995) Expression of transforming growth factor type III receptor in vascular endothelial cells increases their responsiveness to transforming growth factor β2. J Biol Chem 270:13567–13572

    Article  CAS  PubMed  Google Scholar 

  • Scandura JM, Boccuni P, Massague J et al (2004) Transforming growth factor β-induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation. PNAS 101(42):15231–15236

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schmid P, Cox D, Bilbe G et al (1991) Differential expression of TGF-β1, β2 and β3 genes during mouse embryogenesis. Development 111:117–130

    CAS  PubMed  Google Scholar 

  • Sekelsky JJ, Newfeld SJ, Raftery LA et al (1995) Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics 139:1347–1358

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shi Y, Massague J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113(6):685–700

    Article  CAS  PubMed  Google Scholar 

  • Sing GK, Keller JR, Ellingsworth LR et al (1988) Transforming growth factor beta selectively inhibits normal and leukemic human bone marrow cell growth in vitro. Blood 72(5):1504–1511

    CAS  PubMed  Google Scholar 

  • Sirard C, de la Pompa JL, Elia A et al (1998) The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev 12:107–119

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sirard C, Kim S, Mirtsos C et al (2000) Targeted disruption in murine cells reveals variable requirement for Smad4 in transforming growth factor β-related signaling. J Biol Chem 275:2063–2070

  • Sitnicka E, Ruscetti FW, Priestley GV et al (1996) Transforming growth factor beta 1 directly and reversibly inhibits the initial cell divisions of long-term repopulating hematopoietic stem cells. Blood 88(1):82–88

    CAS  PubMed  Google Scholar 

  • Söderberg SS, Karlsson G, Karlsson S (2009) Complex and content dependent regulation of hematopoiesis by TGF-beta superfamily signaling. Ann N Y Acad Sci 1176:55–69

    Article  PubMed  Google Scholar 

  • Sporn MB, Roberts AB, Wakefield LM et al (1987) Some recent advances in the chemistry and biology of transforming gowth factor-beta. J Cell Biol 105:1039–1045

    Article  CAS  PubMed  Google Scholar 

  • Stenvers KL, Tursky ML, Harder KW et al (2003) Heart and liver defects and reduced transforming growth factor β2 sensitivity in transforming growth factor β type III receptor deficient embryos. Mol Cell Biol 23:4371–4385

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stuhlmeier KM, Pollaschek C (2004) Differential effect of transforming growth factor β (TGF-β) on the genes encoding hyaluronan synthases and utilization of the p38 MAPK pathway in TGF-β-induced hyaluronan synthase 1 activation. J Biol Chem 279(10):8753–8760

    Article  CAS  PubMed  Google Scholar 

  • Takaesu G, Ninomiya-Tsuji J, Kishida S et al (2001) Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB 2 translocation in the IL-1 signaling pathway. Mol Cell Biol 21(7):2475–2484

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Takaku K, Miyoshi H, Matsunaga A et al (1999) Gastric and duodenal polyps in Smad4 (Dpc4) knockout mice. Cancer Res 59:6113–6117

    CAS  PubMed  Google Scholar 

  • Ten Dijke P, Hill CS (2004) New insights into TGF-beta-Smadsignalling. Trends BiochemSci 29(5):265–273

    Article  Google Scholar 

  • Tsukazaki T, Chiang TA, Davison AF et al (1998) SARA, a FYVE domain protein that recruits Smad2 to the TGFβ receptor. Cell 95:779–791

    Article  CAS  PubMed  Google Scholar 

  • Utsugisawa T, Moody JL, Aspling M et al (2006) A road map toward defining the role of Smad signaling in hematopoietic stem cells. Stem Cells 24:1128–1136

    Article  CAS  PubMed  Google Scholar 

  • Veiby OP, Jacobsen FW, Cui L et al (1996) The flt3 ligand promotes the survival of primitive hemopoietic progenitor cells with myeloid as well as B lymphoid potential. Suppression of apoptosis and counteraction by TNF-alpha and TGF-beta. J Immunol 157(7):2953–2960

    CAS  PubMed  Google Scholar 

  • Wada T, Penninger JM (2004) Mitogen-activated protein kinases in apoptosis regulation. Oncogene 23:2838–2849

    Article  CAS  PubMed  Google Scholar 

  • Walsh S, Jefferiss C, Stewart K et al (2003) TGFbeta1 limits the expansion of the osteoprogenitor fraction in cultures of human bone marrow stromal cells. Cell Tissue Res 311:187–198

    CAS  PubMed  Google Scholar 

  • Wang L, Kwak JH, Kim SI et al (2004) Transforming growth factor-β1 stimulates vascular endothelial growth factor 164 via mitogen-activated protein kinase kinase 3-p38α and p38δ mitogen-activated protein kinase-dependent pathway in murine mesangial cells. J BiolChem 279:33213–33219

    CAS  Google Scholar 

  • Wrana JL (2009) The secret life of Smad4. Cell 136:13–14

    Article  CAS  PubMed  Google Scholar 

  • Wu G, Chen YG, Ozdamar B et al (2000) Structural basis of Smad2 recognition by the Smad anchor for receptor activation. Science 287:92–97

    Article  CAS  PubMed  Google Scholar 

  • Wu JW, Fairman R, Penry J et al (2001) Formation of a stable heterodimer between Smad2 and Smad4. J Biol Chem 276:20688–20694

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Brodie SG, Yang X et al (2000) Haploid loss of the tumor suppressor Smad4/Dpc4 initiates gastric polyposis and cancer in mice. Oncogene 19(15):1868–1874

    Article  CAS  PubMed  Google Scholar 

  • Xu L, Kang Y, Col S et al (2002) Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus. Mol Cell 10(2):271–282

    Article  CAS  PubMed  Google Scholar 

  • Yamazaki S, Iwama A, Takayanagi S et al (2009) TGF-β as a candidate bone marrow niche signal to induce hematopoietic stem cell hibernation. Blood 113(6):1250–1256

    Article  CAS  PubMed  Google Scholar 

  • Yang X, Li C, Xu X et al (1998) The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice. PNAS 95:3667–3672

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang Y, Feng XH, Derynck R (1998) Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-β-induced transcription. Nature 394:909–913

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Wang W, Hayashi Y et al (2003) A role for MEK kinase 1 in TGF-β/activin-induced epithelium movement and embryonic eyelid closure. EMBO J 22:4443–4454

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Vaidya, A., Kale, V.P. TGF-β signaling and its role in the regulation of hematopoietic stem cells. Syst Synth Biol 9, 1–10 (2015). https://doi.org/10.1007/s11693-015-9161-2

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