Hematopoiesis Flashcards
What is Hemopoiesis?
The process through which formed elements of the blood are produced is called hematopoiesis
Some books refer to as Heimopoiesis
What are formed elements? What is the function?
Vital role in normal functioning of human being
- erythrocytes
- leukocytes
- pletelets
What are totipotent cells? Where is it found?
Ability to develop into all tissu3s
Embryonic
-endoderm, mesoderm, ectoderm
Extra-embryonic
-placental, amnion, chorion
What does pluripotent mean?
Ability of the body to develop into all cells & tissues of the body
— 210 differentiated adult cell types
What is multipotent ?
Ability to develop into a small number of different cell types
What is unipotent?
Ability to develop into a single cell type
What are hematopoietic stem cells(HSC)?
Gives rise to multiple colonies of progenitor stem cells
What are the types of progenitor cells(PC)?
- common myeloid progenitor cells. (CMP) cells)
- common lymphoid progenitor cells (CLP) cells
Previously called colony forming 7nits
CMP differentiates into single cell line- restricted progenitors
-(CFU-GEMM) —> granulocytes, erythrocytes, monocytes, megakaryocytes
- CLP differentiated into T cells, B cells and NK cells
- Precursor cells- morphologically distinct, no self renewal
Summarize hematopoiesis
Erythrocytes & leukocytes are formed in several organs before differentiation of the bone marrow
-yolk sac phase- hematopoiesis begins the 3rd week of gestation- formation of “blood islands” (3-8 weeks)
- hepatic phase- major blood forming organ in second trimester
- bone marrow phase- begins during second trimester as well (also involves other lymphatic tissues)
Where does hemopoiesid occur after birth?
Only in the bone marrow
What are HSCs?
HSCs reside in the cavit of long & axial bones, surrounded by stroke.
Stroma: made of cells derived from mesenchymal stem cells- give rise to
- fibroblasts
- adipocytes
- endothelial cells
- Osteoblasts
Stroma is necessary to suort the hematopoietic stem cells
What is a stem cell niche?
A spatial structure (micro environment) in which HSCs are housed and maintained by allowing self renewal in the absence of differentiation
What are the functions of stem cell line?
- storage of quiescent stem cells
- self Renewal
- inhibition of differentiation
Where is stem cell (endosteal) niche found?
Anatoical location: Epiphyseal areas (spongy bone or “cancellous bone”)
Stem cells are closely associated with the osteoblasts
What is the significance of a vascular niche?
- Quiescent HSCs detach from the endosteal niche and migrate towards the center of the bone marrow to the vascular zone from where they establish hematopoiesis
- Thus specific site where endothelial cells, fibroblasts and adipocytes are found is called the vascular niche, as opposed to endosteal niche
- Collectively, these two niches strongly cooperate to balance HSC quiescence, self-renewing activity, as well as production of early progenitors
Contrast endosteal and vascular niches
Vascular niches: site of proliferation of the multi potent progenitors
Endosteal niche: HSC in contact with osteoblasts lining with endosteum. Osteoblasts regulate the number and the fate of the HSC at the specific niche
What are the functions of vascular niches?
- Support and promote the differentiation & maturation of progenitors into formed elements
- Secretion of growth factors by stromal cells
Describe bone marrow structure
- Structure: reticular fibers, veins, arteries, sinusoids (type of capillaries), islands of cells
- Red marrow: active hematopoiesis
- Yellow marrow: fat, capillaries, retifular cells, inactive hematopoiesis
What do growth factors regulate?
Regulate proliferation & maturation
Progenitor cells have surface receptors for specific cytokines and growth factors (glycoproteins)
Hematopoietic cells will die unless exposed to growth factors
What are erythropoietins(EPO)?
Produced by kidneys increase erythrocyte precursors
What are thrombopoietin (TPO)?
Hormone from liver stimulates thrombocytes formation
What are cytokines?
Local hormones of bone marrow
- produced by some marrow cells to stimulate proliferation in other marrow cells
- colony stimulating factor (CSF) & interleukin stimulate leukocyte production
What is myelopoiesis?
Erythropoiesis
-formation of erythrocytes
Granulocytopouesis
-formation of granulocytes
Monocytopoiesis
-formation of monocytes
Thrombopoiiesis
-formation of thrombocytes(platelets)
What is lymphopoiesis?
Formation of lymphocytes
What simulates erythropoiesis ?
Erythrocyte formation, called erythropoiesis, occurs in adult red bone marrow of certain bones
The main stimulates fir erythropoiesis is hypoxia
Erythropoietin- produced by kidney
Explain erythropoiesis
- Proerythroblast 14- 19 um, no hemoglobin, large nucleus, basophilic cytoplasm
- Basophilic (early) erythroblast: 12- 17 um, some hemoglobin, condensing nucleus
- Polychromatophilic erythroblast: 12-15 um, “muddy” cytoplasm
- Orthochromatophilic (late) erythroblast(normalblast): 8-12 um, increased hemoglobin
- Reticulocyte: 7-8 um, no nucleus, sine ribosomes (blue with freshly blue stain))
- Erythrocyte: 7-8 um, only hemoglobin, no ribosomes
Explain granolopoiesis (granulocytes formation)
- Myoblasts: common precursor, 12-14 um, no granules, cytoplasmic blebs
- Promyelocyte: 16-24 um, large nucleus, azurophilic granules (not specific)
Nutrophils, eosinophils, or basophilic
- Myelocyte: 10-12 um, condensed founded nucleus, specific granules
- Metamyelocyte: kidney-shaped nucleus, specific granules
- Band (stab): C-shaped nucleus, specific granules
- Mature form: neutrophil, eosinophil, basophil
How much granulocytes are formed in a day?
- About 800,000 neutrophils, 170,000 eosinophils, 60,000 basophils per day
- Controlled by cytokines, takes about 11 days
Explain monocytopoiesis
Monocyte formation
- Monoblasts: large, undifferentiated cells
- Promonoblasts: 16-18 um, kidney shaped nucleus, azurophilic granules
- Monocytes: “sky” blue cytoplasm, kidney shaped nucleus
- Enter the circulation, proceed to tissue spaces, differentiate into macrophages
Explain thrombopoietin (platelet formation)
- Controlled by thrombopoietin
- Megakaryoblast: 25:40 um, endomitosis, polyploid (about 32N)
- Megakaryocyte: 40-100 um, large multi-lobed nucleus
- Platelets are formed from fragments of megekaryote cytoplasm (1000’s per cell)
- Platelet demarcation cells
Explain lymphopoiesis
Lymphocyte formation
- Colony forming units (CFU)- lymphocyte (B= bursa equivalent; T= thymus)
- Lymphoblasts: large, undifferentiated cells
- Prolymphocytes: medium-sized cells, condensing chromatin, no cell surface antigens
- Some migrate from bone marrow to thymus, divide and differentiate to T-cells
- Others remain in bone marrow, differentiate to B-cells , migrate to lymph tissues
What adult stem cell plasticity?
Ability of stem cells to form specialized cell types of other tissues
-useful for cell-based therapies
What are the hematopoietic stem cells?
Neurons and glial stem cells
Skeletal muscle cells
Cardiac muscle cells
Liver cells
What are the bone marrow stromal cells?
Cardiac muscle cells
Skeletal muscle cells
What are the neural stem cells?
Blood cells
Skeletal muscle cells
What are the neural stem cells?
Blood cells
Skeletal muscle cells
