Stam Cell Niche


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Stam Cell Niche

  1. 1. Stem Cell Niche Department of Hematology School of Medical Sciences Najmaldin saki Tarbiat Modares
  3. 3. Cell fates available to a stem cell Quiesce Differentiate Self-renew Apoptose
  4. 4. Self-renewal or differentiation
  5. 5. Ratio in BM : 1̸10000 to 1̸100000 Characteristic: Mobilizing: Stemness: Sca-1 G-CSF or rh G-CSF Thy.1 LOW Jagged-1 M-CSF Lin-(HLA-DR, CD71, CD45 SCF N-Cadherin RA,CD38) IL3  rTpo(C-MPL) Tpo CD133+ MIP-1α CD34+ CD117+
  6. 6. Clathrin-Coated pits ED Cells: VWF Ulex europeaus CD22 Col IV Ab CD34 Lam VCAM1 Selectin E CD34+ CD14+ CD45- SDF-1 IL6
  7. 7. Characteristic: receptor for: Alp + Nerve growth factor CD10+ CD13+ HLA I Alpha smoth-muscle actin Vementin Laminin Fibronectin Coll I,III,IV CD34-
  8. 8.  BM reticular cells ………..Adipocyte Starvation Saturated fatty acid Express: Maturin in vitro inhibited by: Leptin IL1 & IL11 Osteocalsin Prolactin receptor VEGF Leptin vs EPO Stem cell erythroied
  9. 9. CD14- Secret: CD34- Secret: GM-CSF CD45- Coll M-CSF VCAM-1+ Fibrinectin CSF Laminin IL6 α-smooth muscle protien(ASP) α-smooth muscle actin(ASA) LIF Proteog Receptor for : glycopro bFGF PDGF EGF TGFβ
  10. 10. Markers: markers of primitive human marrow stromal cells and their CD34- more differentiated progeny STRO-1+ RANKL Secret: N-cad+ TGFβ osteoblast Spindle shaped N-cadherin positive osteoblast B-FGF N-cad- BMP-2 M-CSF G-CSF GM-CSF IL1 IL6 PTH ALP Wnt/βcatenin Ostepontin(OPN) Osteocalcin Coll fibronectin OPG
  11. 11. CD34+ M-CSF has a critical rol in Osteoclastojenesis STRO-1- TRAP+ RANK CD51+ CD54+ CD68+ Secreat: MMP Catepsin K
  12. 12. Endosteal niche M-CSF & RANKL & OPG niche Vascular IL7
  13. 13. HSC O2 O2 HSC
  14. 14. RANKL/OPG ratio MM CD138 Ob Os OPG RANKL RANK
  15. 15. Enucleation of late-stage erythroblasts leads to the formation of two cells – a reticulocyte and a pyrenocyte
  16. 16. • Notch • Hedgehog • Bmi-1 • Wnt
  17. 17. Extracellular space Wnt adenomatous polyposis coli glycogen synthase kinase 3 APC B-catenin B-catenin GSK3 P NUCLEUS Axin B-catenin B-catenin CYTOPLAS
  18. 18. frizzled-related protein Dickkopf (Dkk) families Extracellular space Wnt inhibitory factor 1 low-density lipoprotein receptor–related Sclerostin(SOST gene product) Wnt protein 5 and 6 (LRP5/6) DKK SOST L L L R Kremen R R P P P NUCLEUS Interaction of the Dkk/LRP complex with kremen internalizes the complex for degradation, thus diminishing the number of Wnt coreceptors available for signaling CYTOPLASM
  19. 19. Wnt L R P Dsh APC B-catenin B-catenin GSK3 B-catenin B-catenin B-catenin Axin
  20. 20. T cell factor/lymphoid enhancer binding factor silencing mediator of retinoid and thyroid receptors and nuclear receptor corepressor B-catenin