HEMA LEC PLT

• Megakaryocytes are under the lineage of common myeloid progenitor cell
• After the pluripotential stem cell, it will differentiate into a common myeloid and common lymphoid progenitor cell
• CFUGEMM - Common myeloid progenitor cell
• Megakaryocyte


  • Largest cells in the bone marrow
  • Possess multiple chromosome copies (polyploid)
  • 30 to 50 µm in diameter
  • Multilobulated nucleus
  • Abundant granular cytoplasm
  • 2-4 megakaryocytes per 10x low-power field
  • Accounts less than 0.5% of all bone marrow cells
  • 1 mature megakaryocyte = 2,000 to 4,000 platelets

  
• CFU-GEMM progenitor that will differentiate into the megakaryocyte and platelet lineage
• Platelets arise from a unique cell of the bone marrow known as megakaryocyte

  
• Transcription gene product GATA1 and FOG1 is in charge of differentiating CFU-GEMM into CFU-Meg and CFU-E
• progenitor cell CFU-MegE will first be differentiated from CFU-GEMM and by the cytokines and interleukins involved for the differentiation into CFU-Meg
• Cytokines and interleukins involved for the differentiation of CFU-GEMM into CFU-Meg are:

  
  

  Thrombopoietin

  Meg-CSF

  Interleukin-3
• Transcription gene MYB activation will differentiate CFU-MegE into CFU-E
• CFU-Meg is more common than these two other megakaryocyte lineage committed progenitors: BFU-Meg and LD-CFU-Meg
• LD-CFU-Meg: Light Density Colony Forming Units Megakaryocyte
• The BFU-Meg will have more daughter cells compared with the CFU-Meg progenitor cell.
• There will be more formation of colonies in BFU-Meg than in CFU-meg
• LD-CFU-Meg: - Undergoes unique the type of mitosis which is endoreduplication or endomitosis
• GATA 1 – globin transcription factor 1 • FOG1 – friend of GATA; transcription factor or control gene which facilitates and helps for the function of GATA 1.
• Megakaryocyte


  • Largest cells in the bone marrow
  • Possess multiple chromosome copies (polyploid)
  • 30 to 50 µm in diameter
  • Multilobulated nucleus
  • Abundant granular cytoplasm
  • 2-4 megakaryocytes per 10x low-power field
  • Accounts less than 0.5% of all bone marrow cells
  • 1 mature megakaryocyte = 2,000 to 4,000 platelets

  
• Platelets arise from a unique cell of the bone marrow known as megakaryocyte

  
• The nucleus and the cytoplasm of the megakaryocyte will actually vary depending on its maturation stage

  
• There will only be few megakaryocytes to be seen during a microscopic examination since it has a large diameter compared to other cells in the BM
• Megakaryoctes offer their life to the platelets
• The megakaryocyte will dissolve once it sheds off its cytoplasm and will eventually lead to the formation of platelets

  
• Megakaryocytopoiesis


  The process of megakaryocyte formation and development
• Progenitor cells in megakaryocytopoiesis

  • CFU-GEMM
  • CFU-MegE
  • CFU-Meg
  • CFU-E

  
• GATA 1


  Globin transcription factor 1
• FOG1


  Friend of GATA; transcription factor or control gene which facilitates and helps for the function of GATA 1
• RUNX1


  Mediates the switch from mitosis to endomitosis and suppresses the rho/ROCK signaling pathway
• Endomitosis


  A form of mitosis that lacks telophase and cytokinesis, therefore it is not capable of dividing into two daughter cells

  
• Rho/ROCK signaling pathway


  The pathway needed for cytokinesis to take place

  
• RUNX1 suppresses the rho/ROCK signaling pathway in order that cytokinesis will be inhibited and will not take into place
• NF-E2


  Transcription gene factor that influences the maturation and differentiation of terminal megakaryocytes
• Megakaryocytes employ their multiple DNA copies to synthesize abundant cytoplasm which ultimately differentiates into platelet

  
• As the size of the cytoplasm increases, this will be shed off primarily before it becomes platelets

  
• The platelet will be shed off and will go into the circulation
• Diploid cell


  Normal mitosis
• Polyploid cell


  Endomitosis; division happens within the duplication of chromosomes; division is with the nucleus and not with the cytoplasm

  
• Megakaryocyte committed progenitors


  • BFU-Meg
  • CFU-Meg
  • LD-CFU-Meg
• BFU-Meg and CFU-Meg undergo mitosis, with BFU-Meg producing hundreds of colonies and CFU-Meg producing dozens of colonies
• The function of RUNX1 converts the mitosis process into endomitosis in the LD-CFU-Meg stage
• Megakaryoblast (MK-I)


  The earliest precursor and the most immature recognizable cell in the megakaryocyte lineage