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
  2. 2. CLP GMP HSCs CMP MKEP MSCs
  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

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