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Notch Signaling Mediates the Age-Associated Decrease in Adhesion of Germline Stem Cells to the Niche


Aging is frequently associated with a decline in the size of stem cell pools, but little is known regarding the molecular mechanisms underlying this process. Here, we report that Notch signaling is increased in GSCs as they age, and this promotes their removal from the niche in an E-cadherin dependent manner. In contrast to GSCs, niche cells exhibit decreased Notch signaling with age; Notch signaling in these cells controls niche integrity, and consequently GSC retention. While Notch signaling in the niche is regulated by insulin signaling, Notch signaling in GSCs is controlled by Sex lethal, an RNA-binding protein. These results imply that Notch signaling is regulated in a cell-type-dependent manner, and coordination between GSCs and their niche facilitates the removal of cells from the niche during the aging process.


Vyšlo v časopise: Notch Signaling Mediates the Age-Associated Decrease in Adhesion of Germline Stem Cells to the Niche. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004888
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004888

Souhrn

Aging is frequently associated with a decline in the size of stem cell pools, but little is known regarding the molecular mechanisms underlying this process. Here, we report that Notch signaling is increased in GSCs as they age, and this promotes their removal from the niche in an E-cadherin dependent manner. In contrast to GSCs, niche cells exhibit decreased Notch signaling with age; Notch signaling in these cells controls niche integrity, and consequently GSC retention. While Notch signaling in the niche is regulated by insulin signaling, Notch signaling in GSCs is controlled by Sex lethal, an RNA-binding protein. These results imply that Notch signaling is regulated in a cell-type-dependent manner, and coordination between GSCs and their niche facilitates the removal of cells from the niche during the aging process.


Zdroje

1. Drummond-BarbosaD (2008) Stem cells, their niches and the systemic environment: an aging network. Genetics 180: 1787–1797.

2. DecottoE, SpradlingAC (2005) The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals. Dev Cell 9: 501–510.

3. WangL, LiZ, CaiY (2008) The JAK/STAT pathway positively regulates DPP signaling in the Drosophila germline stem cell niche. J Cell Biol 180: 721–728.

4. ViedC, HorabinJI (2001) The sex determination master switch, Sex-lethal, responds to Hedgehog signaling in the Drosophila germline. Development 128: 2649–2660.

5. LiL, XieT (2005) Stem cell niche: structure and function. Annu Rev Cell Dev Biol 21: 605–631.

6. HeS, NakadaD, MorrisonSJ (2009) Mechanisms of stem cell self-renewal. Annu Rev Cell Dev Biol 25: 377–406.

7. XieT (2013) Control of germline stem cell self-renewal and differentiation in the Drosophila ovary: concerted actions of niche signals and intrinsic factors. Wiley Interdiscip Rev Dev Biol 2: 261–273.

8. WongMD, JinZ, XieT (2005) Molecular mechanisms of germline stem cell regulation. Annu Rev Genet 39: 173–195.

9. Spradling AC (1993) Developmental genetics of oogenesis In: Martinez-Arias MBaA, editor. New York: Cold Spring Harbor Laboratory Press. pp. 1–70.

10. ChenS, WangS, XieT (2011) Restricting self-renewal signals within the stem cell niche: multiple levels of control. Curr Opin Genet Dev

11. KirillyD, XieT (2007) The Drosophila ovary: an active stem cell community. Cell Res 17: 15–25.

12. SongX, XieT (2002) DE-cadherin-mediated cell adhesion is essential for maintaining somatic stem cells in the Drosophila ovary. Proc Natl Acad Sci U S A 99: 14813–14818.

13. XieT, SpradlingAC (2000) A niche maintaining germ line stem cells in the Drosophila ovary. Science 290: 328–330.

14. FiuzaUM, AriasAM (2007) Cell and molecular biology of Notch. J Endocrinol 194: 459–474.

15. LiuJ, SatoC, CerlettiM, WagersA (2010) Notch signaling in the regulation of stem cell self-renewal and differentiation. Curr Top Dev Biol 92: 367–409.

16. SongX, CallGB, KirillyD, XieT (2007) Notch signaling controls germline stem cell niche formation in the Drosophila ovary. Development 134: 1071–1080.

17. WardEJ, ShcherbataHR, ReynoldsSH, FischerKA, HatfieldSD, et al. (2006) Stem cells signal to the niche through the Notch pathway in the Drosophila ovary. Curr Biol 16: 2352–2358.

18. TakeuchiH, HaltiwangerRS (2010) Role of glycosylation of Notch in development. Semin Cell Dev Biol 21: 638–645.

19. BrettJO, RenaultVM, RafalskiVA, WebbAE, BrunetA (2011) The microRNA cluster miR-106b∼25 regulates adult neural stem/progenitor cell proliferation and neuronal differentiation. Aging (Albany NY) 3: 108–124.

20. D'AmarioD, Cabral-Da-SilvaMC, ZhengH, FioriniC, GoichbergP, et al. (2011) Insulin-like growth factor-1 receptor identifies a pool of human cardiac stem cells with superior therapeutic potential for myocardial regeneration. Circ Res 108: 1467–1481.

21. RenaultVM, RafalskiVA, MorganAA, SalihDA, BrettJO, et al. (2009) FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell 5: 527–539.

22. ThumT, HoeberS, FroeseS, KlinkI, StichtenothDO, et al. (2007) Age-dependent impairment of endothelial progenitor cells is corrected by growth-hormone-mediated increase of insulin-like growth-factor-1. Circ Res 100: 434–443.

23. HsuHJ, Drummond-BarbosaD (2009) Insulin levels control female germline stem cell maintenance via the niche in Drosophila. Proc Natl Acad Sci U S A 106: 1117–1121.

24. HsuHJ, Drummond-BarbosaD (2011) Insulin signals control the competence of the Drosophila female germline stem cell niche to respond to Notch ligands. Dev Biol 350: 290–300.

25. LaFeverL, Drummond-BarbosaD (2005) Direct control of germline stem cell division and cyst growth by neural insulin in Drosophila. Science 309: 1071–1073.

26. HsuHJ, LaFeverL, Drummond-BarbosaD (2008) Diet controls normal and tumorous germline stem cells via insulin-dependent and -independent mechanisms in Drosophila. Dev Biol 313: 700–712.

27. JinZ, KirillyD, WengC, KawaseE, SongX, et al. (2008) Differentiation-defective stem cells outcompete normal stem cells for niche occupancy in the Drosophila ovary. Cell Stem Cell 2: 39–49.

28. YangSA, WangWD, ChenCT, TsengCY, ChenYN, et al. (2013) FOXO/Fringe is necessary for maintenance of the germline stem cell niche in response to insulin insufficiency. Dev Biol 382: 124–135.

29. de CelisJF, Garcia-BellidoA (1994) Modifications of the notch function by Abruptex mutations in Drosophila melanogaster. Genetics 136: 183–194.

30. KaiT, SpradlingA (2003) An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells. Proc Natl Acad Sci U S A 100: 4633–4638.

31. Van DorenM, WilliamsonAL, LehmannR (1998) Regulation of zygotic gene expression in Drosophila primordial germ cells. Curr Biol 8: 243–246.

32. PanL, ChenS, WengC, CallG, ZhuD, et al. (2007) Stem cell aging is controlled both intrinsically and extrinsically in the Drosophila ovary. Cell Stem Cell 1: 458–469.

33. McGuireSE, MaoZ, DavisRL (2004) Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila. Sci STKE 2004: pl6.

34. YangX, GongY, TangY, LiH, HeQ, et al. (2013) Spry1 and Spry4 differentially regulate human aortic smooth muscle cell phenotype via Akt/FoxO/myocardin signaling. PLoS One 8: e58746.

35. FurriolsM, BrayS (2001) A model Notch response element detects Suppressor of Hairless-dependent molecular switch. Current Biology 11: 60–64.

36. PennJK, SchedlP (2007) The master switch gene sex-lethal promotes female development by negatively regulating the N-signaling pathway. Dev Cell 12: 275–286.

37. BernsteinM, ClineTW (1994) Differential effects of Sex-lethal mutations on dosage compensation early in Drosophila development. Genetics 136: 1051–1061.

38. HagerJH, ClineTW (1997) Induction of female Sex-lethal RNA splicing in male germ cells: implications for Drosophila germline sex determination. Development 124: 5033–5048.

39. ChauJ, KulnaneLS, SalzHK (2012) Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis. Proceedings of the National Academy of Sciences 109: 9465–9470.

40. Noord-ZaadstraBMv, LoomanCW, AlsbachH, HabbemaJD, VeldeERt, et al. (1991) Delaying childbearing: effect of age on fecundity and outcome of pregnancy. BMJ 302: 1361–1365.

41. JangYC, SinhaM, CerlettiM, Dall'OssoC, WagersAJ (2011) Skeletal Muscle Stem Cells: Effects of Aging and Metabolism on Muscle Regenerative Function. Cold Spring Harbor Symposia on Quantitative Biology 76: 101–111.

42. GiachinoC, TaylorV (2014) Notching up neural stem cell homogeneity in homeostasis and disease. Front Neurosci 8: 32.

43. ScaffidiP, MisteliT (2008) Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat Cell Biol 10: 452–459.

44. MusichPR, ZouY (2009) Genomic instability and DNA damage responses in progeria arising from defective maturation of prelamin A. Aging (Albany NY) 1: 28–37.

45. WoodburyD, ReynoldsK, BlackIB (2002) Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res 69: 908–917.

46. KleinAM, SimonsBD (2011) Universal patterns of stem cell fate in cycling adult tissues. Development 138: 3103–3111.

47. StineRR, MatunisEL (2013) Stem cell competition: finding balance in the niche. Trends Cell Biol 23: 357–364.

48. KaoS-H, TsengC-Y, WanC-L, SuY-H, HsiehC-C, et al. (2014) Aging and insulin signaling differentially controls normal and tumorous germline stem cells. Aging cell under revision

49. KavianN, ServettazA, WeillB, BatteuxF (2012) New insights into the mechanism of notch signalling in fibrosis. Open Rheumatol J 6: 96–102.

50. AvilaFW, EricksonJW (2007) Drosophila JAK/STAT pathway reveals distinct initiation and reinforcement steps in early transcription of Sxl. Curr Biol 17: 643–648.

51. ZhaoR, XuanY, LiX, XiR (2008) Age-related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila. Aging cell 7: 344–354.

52. BellLR, HorabinJI, SchedlP, ClineTW (1991) Positive autoregulation of sex-lethal by alternative splicing maintains the female determined state in Drosophila. Cell 65: 229–239.

53. BellLR, MaineEM, SchedlP, ClineTW (1988) Sex-lethal, a Drosophila sex determination switch gene, exhibits sex-specific RNA splicing and sequence similarity to RNA binding proteins. Cell 55: 1037–1046.

54. MeshorerE, SoreqH (2002) Pre-mRNA splicing modulations in senescence. Aging cell 1: 10–16.

55. Yang S-A, Wang W-D, Chen C-T, Tseng C-Y, Chen Y-N, et al. (2013) FOXO/Fringe is necessary for maintenance of the germline stem cell niche in response to insulin insufficiency Dev Biol under revision

56. McKearinD, SpradlingAC (1990) bag-of-marbles: a Drosophila gene required to initiate both male and female gametogenesis. Genes & Development 4: 2242–2251.

57. HingHK, SunX, Artavanis-TsakonasS (1994) Modulation of wingless signaling by Notch in Drosophila. Mechanisms of Development 47: 261–268.

58. IrvineKD, WieschausE (1994) fringe, a Boundary-specific signaling molecule, mediates interactions between dorsal and ventral cells during Drosophila wing development. Cell 79: 595–606.

59. CorreiaT, PapayannopoulosV, PaninV, WoronoffP, JiangJ, et al. (2003) Molecular genetic analysis of the glycosyltransferase Fringe in Drosophila. Proc Natl Acad Sci U S A 100: 6404–6409.

60. ChoiNH, LucchettaE, OhlsteinB (2011) Nonautonomous regulation of Drosophila midgut stem cell proliferation by the insulin-signaling pathway. Proc Natl Acad Sci U S A 108: 18702–18707.

61. HousdenBE, MillenK, BraySJ (2012) Drosophila Reporter Vectors Compatible with PhiC31 Integrase Transgenesis Techniques and Their Use to Generate New Notch Reporter Fly Lines. G3 (Bethesda) 2: 79–82.

62. YanD, Neumüller RalphA, BucknerM, AyersK, LiH, et al. (2014) A Regulatory Network of Drosophila Germline Stem Cell Self-Renewal. Developmental Cell 28: 459–473.

63. KaiT, WilliamsD, SpradlingAC (2005) The expression profile of purified Drosophila germline stem cells. Dev Biol 283: 486–502.

64. SpradlingAC, RubinGM (1982) Transposition of cloned P elements into Drosophila germ line chromosomes. Science 218: 341–347.

65. XuT, RubinGM (1993) Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117: 1223–1237.

66. LeeT, LuoL (1999) Mosaic Analysis with a Repressible Cell Marker for Studies of Gene Function in Neuronal Morphogenesis. Neuron 22: 451–461.

67. Drummond-BarbosaD, SpradlingAC (2001) Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. Dev Biol 231: 265–278.

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