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Stem Cells and Calcium Signaling

  • Fernanda M. P. Tonelli
  • Anderson K. Santos
  • Dawidson A. Gomes
  • Saulo L. da Silva
  • Katia N. Gomes
  • Luiz O. Ladeira
  • Rodrigo R. Resende
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 740)

Abstract

The increasing interest in stem cell research is linked to the promise of developing treatments for many lifethreatening, debilitating diseases, and for cell replacement therapies. However, performing these therapeutic innovations with safety will only be possible when an accurate knowledge about the molecular signals that promote the desired cell fate is reached. Among these signals are transient changes in intracellular Ca2+ concentration [Ca2+]i. Acting as an intracellular messenger, Ca2+ has a key role in cell signaling pathways in various differentiation stages of stem cells. The aim of this chapter is to present a broad overview of various moments in which Ca2+-mediated signaling is essential for the maintenance of stem cells and for promoting their development and differentiation, also focusing on their therapeutic potential.

Keywords

Calcium transients Embryonic stem cells GPCR and RTK receptors Calcium signaling Stem cells differentiation 

Abbreviations

7TMS

7-transmembrane segment receptor

Akt

Protein kinase B

AM

Amplitude modulation

BDNF

Brain-derived neurotrophic factor

BMP

Bone morphogenetic protein

BMP4

Bone morphogenetic protein 4

CaMK

Calcium/calmodulin dependent kinase protein

CaR

Calcium sensing receptor

cAMP

Cyclic adenosine monophosphate

cGMP

Cyclic guanosine monophosphate

CREB

Binding element responsive to cAMP

DAG

Diacylglycerol

DKK1

Dickkopf 1

ECC

Embryonic carcimona cells

ECM

Extracellular matrix

ELK

Eph-related tyrosine kinase

ER

Endoplasmatic reticulum

ERK

Extracellular-signal-regulated kinase

ESC

Embryonic stem cells

ExEn

Extraembryonic endoderm

FGF

Fibroblast growth factor

FGF1

Fibroblast growth factor 1

FGF2

Fibroblast growth factor 2

FL

Fluorescein

FM

Frequency modulation

FZD

Frizzled

GFP

Green fluorescent protein

GPCR

G protein-coupled receptor

hESC

Human embryonic stem cell

hHSC

Human hematopoietic stem cell

hMSC

Human mesenchymal stem cell

HSC

Hematopoietic stem cell

ICM

Inner cell mass

iMEF

Mitotically inactivated embryonic fibroblast

IP3

Inositol 1,4,5-triphosphate

IP3Rs

Inositol 1,4,5-triphosphate receptors

iPSC

Induced pluripotent stem cell

IVF

in vitro fertilized

JAK

Janus kinase

Klf4

Gut-enriched Krüppel-like factor

LIF

Leukemia inhibitory factor

LPA

Lysophosphatidic acid

MKK3

Mitogen-activated Protein Kinase Kinase 3

MAP

Microtubule-associated protein

MAP1B

Protein association with the microtubule 1B

MAP2

Protein associated with type 2 microtubule

MAPK

Pathways of mitogen-activated protein kinases

MAPKK

MAP kinase kinase

mESC

Mouse embryonic stem cell

NAAD

Nicotinic Acid Adenine Dinucleotide

NANOG

Nanog homeobox

NFAT

Nuclear factors of activated T-cells

NFκB

Nuclear factor κBl

NSC

Neural stem cell

OAP

Oct/octamer-associated protein

OCT-4

Octamer-binding transcription factor 4

PI3K

Phosphoinositide Kinase-3

PIP2

Phosphatidylinositol 4,5-biphosphate

PKA

Protein kinase A

PKC

Protein kinase C

PLC

Phospholipase C

PSC

Pluripotent stem cell

Ras

Rat sarcoma similar to G protein GTPase

Rcn2

Reticulocalbin-2

RyR

Ryanodine receptors

ROC

Receptor-operated channels

RTKs

Receptors tyrosine kinase

Stk40

Serine/threonine kinase 40

SOX2

Sex determining region Y box 2

SR

Sarcoplasmatic reticulum

SOC

Store-operated channels

SSC

Somatic stem cell

STAT3

Signal transducer and activator of transcription 3

Stk40

Serine/threonine kinase 40

TBX3

T-box transcription factor

Tc

Tetracycline

TGF-β

Transforming growth factor-β

TSC

Tumor stem cell

VOCC

Voltage-operated calcium channels

Notes

Acknowledgements

This work was supported by Instituto Nacional de Ciência e Tecnologia de Nanomateriais de Carbono, CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), Brazil. R.R.R, L.O.L., K.N.G., and D.A.G. are grateful for grants from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais), and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior).

References

  1. 1.
    Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1:11–21PubMedCrossRefGoogle Scholar
  2. 2.
    Kawano S, Shoji S, Ichinose S, Yamagata K, Tagami M, Hiraoka M (2002) Characterization of Ca(2+) signaling pathways in human mesenchymal stem cells. Cell Calcium 32:165–174PubMedCrossRefGoogle Scholar
  3. 3.
    Kawano S, Otsu K, Shoji S, Yamagata K, Hiraoka M (2003) Ca(2+) oscillations regulated by Na(+)-Ca(2+) exchanger and plasma membrane Ca(2+) pump induce fluctuations of membrane currents and potentials in human mesenchymal stem cells. Cell Calcium 34:145–156PubMedCrossRefGoogle Scholar
  4. 4.
    Li GR, Sun H, Deng X, Lau CP (2005) Characterization of ionic currents in human mesenchymal stem cells from bone marrow. Stem Cells 23:371–382PubMedCrossRefGoogle Scholar
  5. 5.
    Heubach JF, Graf EM, Leutheuser J, Bock M, Balana B, Zahanich I, Christ T, Boxberger S, Wettwer E, Ravens U (2004) Electrophysiological properties of human mesenchymal stem cells. J Physiol 554:659–672PubMedCrossRefGoogle Scholar
  6. 6.
    Ameen C, Strehl R, Bjorquist P, Lindahl A, Hyllner J, Sartipy P (2008) Human embryonic stem cells: current technologies and emerging industrial applications. Crit Rev Oncol Hematol 65:54–80PubMedCrossRefGoogle Scholar
  7. 7.
    Friel R, van der Sar S, Mee PJ (2005) Embryonic stem cells: understanding their history, cell biology and signalling. Adv Drug Deliv Rev 57:1894–1903PubMedCrossRefGoogle Scholar
  8. 8.
    Callihan P, Mumaw J, Machacek DW, Stice SL, Hooks SB (2011) Regulation of stem cell pluripotency and differentiation by G protein coupled receptors. Pharmacol Ther 129:290–306PubMedCrossRefGoogle Scholar
  9. 9.
    Wakayama T, Tabar V, Rodriguez I, Perry AC, Studer L, Mombaerts P (2001) Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science 292:740–743PubMedCrossRefGoogle Scholar
  10. 10.
    Kane NM, Xiao Q, Baker AH, Luo Z, Xu Q, Emanueli C (2011) Pluripotent stem cell differentiation into vascular cells: a novel technology with promises for vascular re(generation). Pharmacol Ther 129:29–49PubMedCrossRefGoogle Scholar
  11. 11.
    Takayama N, Nishikii H, Usui J, Tsukui H, Sawaguchi A, Hiroyama T, Eto K, Nakauchi H (2008) Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors. Blood 111:5298–5306PubMedCrossRefGoogle Scholar
  12. 12.
    Niwa H (2007) How is pluripotency determined and maintained? Development 134:635–646PubMedCrossRefGoogle Scholar
  13. 13.
    Denker HW (2006) Potentiality of embryonic stem cells: an ethical problem even with alternative stem cell sources. J Med Ethics 32:665–671PubMedCrossRefGoogle Scholar
  14. 14.
    Leandri RD, Archilla C, Bui LC, Peynot N, Liu Z, Cabau C, Chastellier A, Renard JP, Duranthon V (2009) Revealing the dynamics of gene expression during embryonic genome activation and first differentiation in the rabbit embryo with a dedicated array screening. Physiol Genomics 36:98–113PubMedGoogle Scholar
  15. 15.
    Suwinska A, Tarkowski AK, Ciemerych MA (2010) Pluripotency of bank vole embryonic cells depends on FGF2 and activin A signaling pathways. Int J Dev Biol 54:113–124PubMedCrossRefGoogle Scholar
  16. 16.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676PubMedCrossRefGoogle Scholar
  17. 17.
    Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920PubMedCrossRefGoogle Scholar
  18. 18.
    Stadtfeld M, Maherali N, Breault DT, Hochedlinger K (2008) Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2:230–240PubMedCrossRefGoogle Scholar
  19. 19.
    Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458:766–770PubMedCrossRefGoogle Scholar
  20. 20.
    Kim JB, Sebastiano V, Wu G, Arauzo-Bravo MJ, Sasse P, Gentile L, Ko K, Ruau D, Ehrich M, van den Boom D, Meyer J, Hubner K, Bernemann C, Ortmeier C, Zenke M, Fleischmann BK, Zaehres H, Scholer HR (2009) Oct4-induced pluripotency in adult neural stem cells. Cell 136:411–419PubMedCrossRefGoogle Scholar
  21. 21.
    Qin T, Miao XY (2010) Current progress and application prospects of induced pluripotent stem cells. Yi Chuan 32:1205–1214PubMedGoogle Scholar
  22. 22.
    Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ (2008) Disease-specific induced pluripotent stem cells. Cell 134:877–886PubMedCrossRefGoogle Scholar
  23. 23.
    Emdad L, D’Souza SL, Kothari HP, Qadeer ZA, Germano IM (2011) Efficient differentiation of human embryonic and induced pluripotent stem cells into functional astrocytes. Stem Cells Dev. Not available-, ahead of print. doi: 10.1089/scd.2010.0560
  24. 24.
    Bootman MD, Lipp P, Berridge MJ (2001) The organisation and functions of local Ca(2+) signals. J Cell Sci 114:2213–2222PubMedGoogle Scholar
  25. 25.
    Berridge MJ (1998) Neuronal calcium signaling. Neuron 21:13–26PubMedCrossRefGoogle Scholar
  26. 26.
    Sun S, Liu Y, Lipsky S, Cho M (2007) Physical manipulation of calcium oscillations facilitates osteodifferentiation of human mesenchymal stem cells. FASEB J 21:1472–1480PubMedCrossRefGoogle Scholar
  27. 27.
    Gu X, Olson EC, Spitzer NC (1994) Spontaneous neuronal calcium spikes and waves during early differentiation. J Neurosci 14:6325–6335PubMedGoogle Scholar
  28. 28.
    Buonanno A, Fields RD (1999) Gene regulation by patterned electrical activity during neural and skeletal muscle development. Curr Opin Neurobiol 9:110–120PubMedCrossRefGoogle Scholar
  29. 29.
    Ferrari MB, Ribbeck K, Hagler DJ, Spitzer NC (1998) A calcium signaling cascade essential for myosin thick filament assembly in Xenopus myocytes. J Cell Biol 141:1349–1356PubMedCrossRefGoogle Scholar
  30. 30.
    Gu X, Spitzer NC (1995) Distinct aspects of neuronal differentiation encoded by frequency of spontaneous Ca2+ transients. Nature 375:784–787PubMedCrossRefGoogle Scholar
  31. 31.
    Carey MB, Matsumoto SG (1999) Spontaneous calcium transients are required for neuronal differentiation of murine neural crest. Dev Biol 215:298–313PubMedCrossRefGoogle Scholar
  32. 32.
    Gomez TM, Spitzer NC (1999) In vivo regulation of axon extension and pathfinding by growth-cone calcium transients. Nature 397:350–355PubMedCrossRefGoogle Scholar
  33. 33.
    Wong RC, Pera MF, Pebay A (2008) Role of gap junctions in embryonic and somatic stem cells. Stem Cell Rev 4:283–292PubMedCrossRefGoogle Scholar
  34. 34.
    Bootman M, Niggli E, Berridge M, Lipp P (1997) Imaging the hierarchical Ca2+ signalling system in HeLa cells. J Physiol 499(Pt 2):307–314PubMedGoogle Scholar
  35. 35.
    Lipp P, Niggli E (1998) Fundamental calcium release events revealed by two-photon excitation photolysis of caged calcium in Guinea-pig cardiac myocytes. J Physiol 508(Pt 3):801–809PubMedCrossRefGoogle Scholar
  36. 36.
    Yao Y, Choi J, Parker I (1995) Quantal puffs of intracellular Ca2+ evoked by inositol trisphosphate in Xenopus oocytes. J Physiol 482(Pt 3):533–553PubMedGoogle Scholar
  37. 37.
    Cheng H, Lederer WJ, Cannell MB (1993) Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science 262:740–744PubMedCrossRefGoogle Scholar
  38. 38.
    Bootman MD, Berridge MJ (1996) Subcellular Ca2+ signals underlying waves and graded responses in HeLa cells. Curr Biol 6:855–865PubMedCrossRefGoogle Scholar
  39. 39.
    Bootman MD, Berridge MJ, Lipp P (1997) Cooking with calcium: the recipes for composing global signals from elementary events. Cell 91:367–373PubMedCrossRefGoogle Scholar
  40. 40.
    Lautermilch NJ, Spitzer NC (2000) Regulation of calcineurin by growth cone calcium waves controls neurite extension. J Neurosci 20:315–325PubMedGoogle Scholar
  41. 41.
    Spitzer NC, Root CM, Borodinsky LN (2004) Orchestrating neuronal differentiation: patterns of Ca2+ spikes specify transmitter choice. Trends Neurosci 27:415–421PubMedCrossRefGoogle Scholar
  42. 42.
    Resende RR, Alves AS, Britto LR, Ulrich H (2008) Role of acetylcholine receptors in proliferation and differentiation of P19 embryonal carcinoma cells. Exp Cell Res 314:1429–1443PubMedCrossRefGoogle Scholar
  43. 43.
    Resende RR, Gomes KN, Adhikari A, Britto LR, Ulrich H (2008) Mechanism of acetylcholine-induced calcium signaling during neuronal differentiation of P19 embryonal carcinoma cells in vitro. Cell Calcium 43:107–121PubMedCrossRefGoogle Scholar
  44. 44.
    Bird GS, Putney JW Jr (1996) Effect of inositol 1,3,4,5-tetrakisphosphate on inositol trisphosphate-activated Ca2+ signaling in mouse lacrimal acinar cells. J Biol Chem 271: 6766–6770PubMedCrossRefGoogle Scholar
  45. 45.
    Tumelty J, Scholfield N, Stewart M, Curtis T, McGeown G (2007) Ca2+-sparks constitute elementary building blocks for global Ca2+-signals in myocytes of retinal arterioles. Cell Calcium 41:451–466PubMedCrossRefGoogle Scholar
  46. 46.
    Maier LS, Zhang T, Chen L, DeSantiago J, Brown JH, Bers DM (2003) Transgenic CaMKIIdeltaC overexpression uniquely alters cardiac myocyte Ca2+ handling: reduced SR Ca2+ load and activated SR Ca2+ release. Circ Res 92:904–911PubMedCrossRefGoogle Scholar
  47. 47.
    Dolmetsch RE, Lewis RS, Goodnow CC, Healy JI (1997) Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature 386:855–858PubMedCrossRefGoogle Scholar
  48. 48.
    Dolmetsch RE, Xu K, Lewis RS (1998) Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392:933–936PubMedCrossRefGoogle Scholar
  49. 49.
    Li W, Llopis J, Whitney M, Zlokarnik G, Tsien RY (1998) Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression. Nature 392:936–941PubMedCrossRefGoogle Scholar
  50. 50.
    Lo Turco JJ, Kriegstein AR (1991) Clusters of coupled neuroblasts in embryonic neocortex. Science 252:563–566PubMedCrossRefGoogle Scholar
  51. 51.
    Weissman TA, Riquelme PA, Ivic L, Flint AC, Kriegstein AR (2004) Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex. Neuron 43:647–661PubMedCrossRefGoogle Scholar
  52. 52.
    Cotrina ML, Lin JH, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, Kang J, Naus CC, Nedergaard M (1998) Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci USA 95:15735–15740PubMedCrossRefGoogle Scholar
  53. 53.
    Kihara AH, Paschon V, Akamine PS, Saito KC, Leonelli M, Jiang JX, Hamassaki DE, Britto LR (2008) Differential expression of connexins during histogenesis of the chick retina. Dev Neurobiol 68:1287–1302PubMedCrossRefGoogle Scholar
  54. 54.
    Kihara AH, Santos TO, Osuna-Melo EJ, Paschon V, Vidal KS, Akamine PS, Castro LM, Resende RR, Hamassaki DE, Britto LR (2010) Connexin-mediated communication controls cell proliferation and is essential in retinal histogenesis. Int J Dev Neurosci 28:39–52PubMedCrossRefGoogle Scholar
  55. 55.
    Cina C, Bechberger JF, Ozog MA, Naus CC (2007) Expression of connexins in embryonic mouse neocortical development. J Comp Neurol 504:298–313PubMedCrossRefGoogle Scholar
  56. 56.
    Resende RR, da Costa JL, Kihara AH, Adhikari A, Lorencon E (2010) Intracellular Ca2+ regulation during neuronal differentiation of murine embryonal carcinoma and mesenchymal stem cells. Stem Cells Dev 19:379–394PubMedCrossRefGoogle Scholar
  57. 57.
    Resende RR, Adhikari A, da Costa JL, Lorencon E, Ladeira MS, Guatimosim S, Kihara AH, Ladeira LO (2010) Influence of spontaneous calcium events on cell-cycle progression in embryonal carcinoma and adult stem cells. Biochim Biophys Acta 1803:246–260PubMedCrossRefGoogle Scholar
  58. 58.
    Natarajan K, Berk BC (2006) Crosstalk coregulation mechanisms of G protein-coupled receptors and receptor tyrosine kinases. Methods Mol Biol 332:51–77PubMedGoogle Scholar
  59. 59.
    Shen P, Larter R (1995) Chaos in intracellular Ca2+ oscillations in a new model for non-excitable cells. Cell Calcium 17:225–232PubMedCrossRefGoogle Scholar
  60. 60.
    Woods NM, Cuthbertson KS, Cobbold PH (1986) Repetitive transient rises in cytoplasmic free calcium in hormone-stimulated hepatocytes. Nature 319:600–602PubMedCrossRefGoogle Scholar
  61. 61.
    Kraus M, Wolf B (1993) Cytosolic calcium oscillators: critical discussion and stochastic modelling. Biol Signals 2:1–15PubMedCrossRefGoogle Scholar
  62. 62.
    Haisenleder DJ, Yasin M, Marshall JC (1997) Gonadotropin subunit and gonadotropin-releasing hormone receptor gene expression are regulated by alterations in the frequency of calcium pulsatile signals. Endocrinology 138:5227–5230PubMedCrossRefGoogle Scholar
  63. 63.
    Chang LW, Spitzer NC (2009) Spontaneous calcium spike activity in embryonic spinal neurons is regulated by developmental expression of the Na+, K+-ATPase beta3 subunit. J Neurosci 29:7877–7885PubMedCrossRefGoogle Scholar
  64. 64.
    Kuczewski N, Porcher C, Ferrand N, Fiorentino H, Pellegrino C, Kolarow R, Lessmann V, Medina I, Gaiarsa JL (2008) Backpropagating action potentials trigger dendritic release of BDNF during spontaneous network activity. J Neurosci 28:7013–7023PubMedCrossRefGoogle Scholar
  65. 65.
    Willoughby D, Cooper DM (2006) Ca2+ stimulation of adenylyl cyclase generates dynamic oscillations in cyclic AMP. J Cell Sci 119:828–836PubMedCrossRefGoogle Scholar
  66. 66.
    Kaang BK, Kandel ER, Grant SGN (1993) Activation of camp-responsive genes by stimuli that produce long-term facilitation in aplysia sensory neurons. Neuron 10:427–435PubMedCrossRefGoogle Scholar
  67. 67.
    Gorbunova YV, Spitzer NC (2002) Dynamic interactions of cyclic AMP transients and spontaneous Ca(2+) spikes. Nature 418:93–96PubMedCrossRefGoogle Scholar
  68. 68.
    Bacskai BJ, Hochner B, Mahaut-Smith M, Adams SR, Kaang BK, Kandel ER, Tsien RY (1993) Spatially resolved dynamics of cAMP and protein kinase A subunits in Aplysia sensory neurons. Science 260:222–226PubMedCrossRefGoogle Scholar
  69. 69.
    Cooper DM, Mons N, Karpen JW (1995) Adenylyl cyclases and the interaction between calcium and cAMP signalling. Nature 374:421–424PubMedCrossRefGoogle Scholar
  70. 70.
    Willoughby D, Cooper DM (2007) Organization and Ca2+ regulation of adenylyl cyclases in cAMP microdomains. Physiol Rev 87:965–1010PubMedCrossRefGoogle Scholar
  71. 71.
    Resende RR, Britto LR, Ulrich H (2008) Pharmacological properties of purinergic receptors and their effects on proliferation and induction of neuronal differentiation of P19 embryonal carcinoma cells. Int J Dev Neurosci 26:763–777PubMedCrossRefGoogle Scholar
  72. 72.
    Ciccolini F, Collins TJ, Sudhoelter J, Lipp P, Berridge MJ, Bootman MD (2003) Local and global spontaneous calcium events regulate neurite outgrowth and onset of GABAergic phenotype during neural precursor differentiation. J Neurosci 23:103–111PubMedGoogle Scholar
  73. 73.
    Bading H (2000) Transcription-dependent neuronal plasticity the nuclear calcium hypothesis. Eur J Biochem 267:5280–5283PubMedCrossRefGoogle Scholar
  74. 74.
    Hardingham GE, Chawla S, Johnson CM, Bading H (1997) Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression. Nature 385:260–265PubMedCrossRefGoogle Scholar
  75. 75.
    Studzinski DM, Callahan RE, Benjamins JA (1999) Increased intracellular calcium alters myelin gene expression in the N20.1 oligodendroglial cell line. J Neurosci Res 57:633–642PubMedCrossRefGoogle Scholar
  76. 76.
    Ferreira-Martins J, Rondon-Clavo C, Tugal D, Korn JA, Rizzi R, Padin-Iruegas ME, Ottolenghi S, De Angelis A, Urbanek K, Ide-Iwata N, D’Amario D, Hosoda T, Leri A, Kajstura J, Anversa P, Rota M (2009) Spontaneous calcium oscillations regulate human cardiac progenitor cell growth. Circ Res 105:764–774PubMedCrossRefGoogle Scholar
  77. 77.
    Uhlen P, Burch PM, Zito CI, Estrada M, Ehrlich BE, Bennett AM (2006) Gain-of-function/Noonan syndrome SHP-2/Ptpn11 mutants enhance calcium oscillations and impair NFAT signaling. Proc Natl Acad Sci USA 103:2160–2165PubMedCrossRefGoogle Scholar
  78. 78.
    Scemes E, Duval N, Meda P (2003) Reduced expression of P2Y1 receptors in connexin43-null mice alters calcium signaling and migration of neural progenitor cells. J Neurosci 23:11444–11452PubMedGoogle Scholar
  79. 79.
    Moreau M, Neant I, Webb SE, Miller AL, Leclerc C (2008) Calcium signalling during neural induction in Xenopus laevis embryos. Philos Trans R Soc Lond B Biol Sci 363:1371–1375PubMedCrossRefGoogle Scholar
  80. 80.
    Leclerc C, Webb SE, Daguzan C, Moreau M, Miller AL (2000) Imaging patterns of calcium transients during neural induction in Xenopus laevis embryos. J Cell Sci 113(Pt 19):3519–3529PubMedGoogle Scholar
  81. 81.
    Swiers G, Patient R, Loose M (2006) Genetic regulatory networks programming hematopoietic stem cells and erythroid lineage specification. Dev Biol 294:525–540PubMedCrossRefGoogle Scholar
  82. 82.
    Theilgaard-Monch K, Jacobsen LC, Borup R, Rasmussen T, Bjerregaard MD, Nielsen FC, Cowland JB, Borregaard N (2005) The transcriptional program of terminal granulocytic differentiation. Blood 105:1785–1796PubMedCrossRefGoogle Scholar
  83. 83.
    May RM (1972) Will a large complex system be stable? Nature 238:413–414PubMedCrossRefGoogle Scholar
  84. 84.
    Kauffman S (1993) The origins of order: self-organization and selection in evolution. Oxford University Press, New YorkGoogle Scholar
  85. 85.
    Aldana M, Cluzel P (2003) A natural class of robust networks. Proc Natl Acad Sci USA 100:8710–8714PubMedCrossRefGoogle Scholar
  86. 86.
    Chang HH, Oh PY, Ingber DE, Huang S (2006) Multistable and multistep dynamics in neutrophil differentiation. BMC Cell Biol 7:11PubMedCrossRefGoogle Scholar
  87. 87.
    Ferrell JE, Xiong W (2001) Bistability in cell signaling: how to make continuous processes discontinuous, and reversible processes irreversible. Chaos 11:227–236PubMedCrossRefGoogle Scholar
  88. 88.
    Xiong W, Ferrell JE Jr (2003) A positive-feedback-based bistable ‘memory module’ that governs a cell fate decision. Nature 426:460–465PubMedCrossRefGoogle Scholar
  89. 89.
    Huang S, Guo YP, May G, Enver T (2007) Bifurcation dynamics in lineage-commitment in bipotent progenitor cells. Dev Biol 305:695–713PubMedCrossRefGoogle Scholar
  90. 90.
    Ying QL, Nichols J, Chambers I, Smith A (2003) BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115:281–292PubMedCrossRefGoogle Scholar
  91. 91.
    Niwa H, Ogawa K, Shimosato D, Adachi K (2009) A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature 460:118–122PubMedCrossRefGoogle Scholar
  92. 92.
    Wei CL, Miura T, Robson P, Lim SK, Xu XQ, Lee MY, Gupta S, Stanton L, Luo Y, Schmitt J, Thies S, Wang W, Khrebtukova I, Zhou D, Liu ET, Ruan YJ, Rao M, Lim B (2005) Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state. Stem Cells 23:166–185PubMedCrossRefGoogle Scholar
  93. 93.
    Dvorak P, Dvorakova D, Koskova S, Vodinska M, Najvirtova M, Krekac D, Hampl A (2005) Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells. Stem Cells 23:1200–1211PubMedCrossRefGoogle Scholar
  94. 94.
    Todorova MG, Fuentes E, Soria B, Nadal A, Quesada I (2009) Lysophosphatidic acid induces Ca2+ mobilization and c-Myc expression in mouse embryonic stem cells via the phospholipase C pathway. Cell Signal 21:523–528PubMedCrossRefGoogle Scholar
  95. 95.
    Schulte G, Bryja V (2007) The Frizzled family of unconventional G-protein-coupled receptors. Trends Pharmacol Sci 28:518–525PubMedCrossRefGoogle Scholar
  96. 96.
    Bhandari DR, Seo KW, Roh KH, Jung JW, Kang SK, Kang KS (2010) REX-1 expression and p38 MAPK activation status can determine proliferation/differentiation fates in human mesenchymal stem cells. PLoS One 5:e10493PubMedCrossRefGoogle Scholar
  97. 97.
    Li L, Sun L, Gao F, Jiang J, Yang Y, Li C, Gu J, Wei Z, Yang A, Lu R, Ma Y, Tang F, Kwon SW, Zhao Y, Li J, Jin Y (2010) Stk40 links the pluripotency factor Oct4 to the Erk/MAPK pathway and controls extraembryonic endoderm differentiation. Proc Natl Acad Sci USA 107:1402–1407PubMedCrossRefGoogle Scholar
  98. 98.
    Jiang H, Grenley MO, Bravo MJ, Blumhagen RZ, Edgar BA (2011) EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila. Cell Stem Cell 8:84–95PubMedCrossRefGoogle Scholar
  99. 99.
    Batts SA, Raphael Y (2007) Transdifferentiation and its applicability for inner ear therapy. Hear Res 227:41–47PubMedCrossRefGoogle Scholar
  100. 100.
    Dalby MJ, Gadegaard N, Tare R, Andar A, Riehle MO, Herzyk P, Wilkinson CD, Oreffo RO (2007) The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater 6:997–1003PubMedCrossRefGoogle Scholar
  101. 101.
    Charbord P, Moore K (2005) Gene expression in stem cell-supporting stromal cell lines. Ann NY Acad Sci 1044:159–167PubMedCrossRefGoogle Scholar
  102. 102.
    Dutt P, Wang JF, Groopman JE (1998) Stromal cell-derived factor-1 alpha and stem cell factor/kit ligand share signaling pathways in hemopoietic progenitors: a potential mechanism for cooperative induction of chemotaxis. J Immunol 161:3652–3658PubMedGoogle Scholar
  103. 103.
    de Boer J, Siddappa R, Gaspar C, van Apeldoorn A, Fodde R, van Blitterswijk C (2004) Wnt signaling inhibits osteogenic differentiation of human mesenchymal stem cells. Bone 34:818–826PubMedCrossRefGoogle Scholar
  104. 104.
    Rizo A, Vellenga E, de Haan G, Schuringa JJ (2006) Signaling pathways in self-renewing hematopoietic and leukemic stem cells: do all stem cells need a niche? Hum Mol Genet 15(Spec No 2):R210–R219PubMedCrossRefGoogle Scholar
  105. 105.
    Clapham DE (2007) Calcium signaling. Cell 131:1047–1058PubMedCrossRefGoogle Scholar
  106. 106.
    Kajiume T, Ninomiya Y, Ishihara H, Kanno R, Kanno M (2004) Polycomb group gene mel-18 modulates the self-renewal activity and cell cycle status of hematopoietic stem cells. Exp Hematol 32:571–578PubMedCrossRefGoogle Scholar
  107. 107.
    Singh V, Mueller U, Freyschmidt-Paul P, Zoller M (2011) Delayed type hypersensitivity-induced myeloid-derived suppressor cells regulate autoreactive T cells. Eur J Immunol 41:2871–2882PubMedCrossRefGoogle Scholar
  108. 108.
    Puceat M, Jaconi M (2005) Ca2+ signalling in cardiogenesis. Cell Calcium 38:383–389PubMedCrossRefGoogle Scholar
  109. 109.
    Park JS, Kim YS, Yoo MA (2009) The role of p38b MAPK in age-related modulation of intestinal stem cell proliferation and differentiation in Drosophila. Aging (Albany NY) 1:637–651Google Scholar
  110. 110.
    Grajales L, Garcia J, Banach K, Geenen DL (2010) Delayed enrichment of mesenchymal cells promotes cardiac lineage and calcium transient development. J Mol Cell Cardiol 48:735–745PubMedCrossRefGoogle Scholar
  111. 111.
    Biteau B, Hochmuth CE, Jasper H (2008) JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3:442–455PubMedCrossRefGoogle Scholar
  112. 112.
    Reim K, Mansour M, Varoqueaux F, McMahon HT, Sudhof TC, Brose N, Rosenmund C (2001) Complexins regulate a late step in Ca2+-dependent neurotransmitter release. Cell 104:71–81PubMedCrossRefGoogle Scholar
  113. 113.
    Kawano S, Otsu K, Kuruma A, Shoji S, Yanagida E, Muto Y, Yoshikawa F, Hirayama Y, Mikoshiba K, Furuichi T (2006) ATP autocrine/paracrine signaling induces calcium oscillations and NFAT activation in human mesenchymal stem cells. Cell Calcium 39:313–324PubMedCrossRefGoogle Scholar
  114. 114.
    Sauka-Spengler T, Bronner-Fraser M (2008) A gene regulatory network orchestrates neural crest formation. Nat Rev Mol Cell Biol 9:557–568PubMedCrossRefGoogle Scholar
  115. 115.
    Winkler DA, Burden FR, Halley JD (2009) Predictive mesoscale network model of cell fate decisions during C. elegans embryogenesis. Artif Life 15:411–421PubMedCrossRefGoogle Scholar
  116. 116.
    Raff MC (1992) Social controls on cell survival and cell death. Nature 356:397–400PubMedCrossRefGoogle Scholar
  117. 117.
    Evan G, Littlewood T (1998) A matter of life and cell death. Science 281:1317–1322PubMedCrossRefGoogle Scholar
  118. 118.
    Baubet V, Le Mouellic H, Campbell AK, Lucas-Meunier E, Fossier P, Brulet P (2000) Chimeric green fluorescent protein-aequorin as bioluminescent Ca2+ reporters at the single-cell level. Proc Natl Acad Sci USA 97:7260–7265PubMedCrossRefGoogle Scholar
  119. 119.
    Brini M, Pinton P, Pozzan T, Rizzuto R (1999) Targeted recombinant aequorins: tools for monitoring [Ca2+] in the various compartments of a living cell. Microsc Res Tech 46:380–389PubMedCrossRefGoogle Scholar
  120. 120.
    Dorsky RI, Sheldahl LC, Moon RT (2002) A transgenic Lef1/beta-catenin-dependent reporter is expressed in spatially restricted domains throughout zebrafish development. Dev Biol 241:229–237PubMedCrossRefGoogle Scholar
  121. 121.
    Li CJ, Heim R, Lu P, Pu Y, Tsien RY, Chang DC (1999) Dynamic redistribution of calmodulin in HeLa cells during cell division as revealed by a GFP-calmodulin fusion protein technique. J Cell Sci 112(Pt 10):1567–1577PubMedGoogle Scholar
  122. 122.
    Torok K, Wilding M, Groigno L, Patel R, Whitaker M (1998) Imaging the spatial dynamics of calmodulin activation during mitosis. Curr Biol 8:692–699PubMedCrossRefGoogle Scholar
  123. 123.
    Groth RD, Mermelstein PG (2003) Brain-derived neurotrophic factor activation of NFAT (nuclear factor of activated T-cells)-dependent transcription: a role for the transcription factor NFATc4 in neurotrophin-mediated gene expression. J Neurosci 23:8125–8134PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Fernanda M. P. Tonelli
    • 3
  • Anderson K. Santos
    • 3
  • Dawidson A. Gomes
    • 2
  • Saulo L. da Silva
    • 3
  • Katia N. Gomes
    • 1
  • Luiz O. Ladeira
    • 3
  • Rodrigo R. Resende
    • 3
    • 1
  1. 1.Nanomaterials Laboratory, Department of Physics, Institute of Exact SciencesFederal University of Minas GeraisBelo HorizonteBrazil
  2. 2.Department of Biochemistry and Immunology, Institute of Biological SciencesFederal University of Minas GeraisBelo HorizonteBrazil
  3. 3.Universidade Federal de São João Del Rei Campus Alto ParaopebaBelo HorizonteBrazil

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