Hematopoiesis

Question 1

What is Hemopoiesis?

Answer 1

The process through which formed elements of the blood are produced is called hematopoiesis

Some books refer to as Heimopoiesis

Question 2

What are formed elements? What is the function?

Answer 2

Vital role in normal functioning of human being

• erythrocytes
• leukocytes
• pletelets

Question 3

What are totipotent cells? Where is it found?

Answer 3

Ability to develop into all tissu3s

Embryonic
-endoderm, mesoderm, ectoderm

Extra-embryonic
-placental, amnion, chorion

Question 4

What does pluripotent mean?

Answer 4

Ability of the body to develop into all cells & tissues of the body
— 210 differentiated adult cell types

Question 5

What is multipotent ?

Answer 5

Ability to develop into a small number of different cell types

Question 6

What is unipotent?

Answer 6

Ability to develop into a single cell type

Question 7

What are hematopoietic stem cells(HSC)?

Answer 7

Gives rise to multiple colonies of progenitor stem cells

Question 8

What are the types of progenitor cells(PC)?

Answer 8

• 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

Question 9

Summarize hematopoiesis

Answer 9

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)

Question 10

Where does hemopoiesid occur after birth?

Answer 10

Only in the bone marrow

Question 11

What are HSCs?

Answer 11

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

Question 12

What is a stem cell niche?

Answer 12

A spatial structure (micro environment) in which HSCs are housed and maintained by allowing self renewal in the absence of differentiation

Question 13

What are the functions of stem cell line?

Answer 13

• storage of quiescent stem cells
• self Renewal
• inhibition of differentiation

Question 14

Where is stem cell (endosteal) niche found?

Answer 14

Anatoical location: Epiphyseal areas (spongy bone or “cancellous bone”)

Stem cells are closely associated with the osteoblasts

Question 15

What is the significance of a vascular niche?

Answer 15

• 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

Question 16

Contrast endosteal and vascular niches

Answer 16

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

Question 17

What are the functions of vascular niches?

Answer 17

• Support and promote the differentiation & maturation of progenitors into formed elements
• Secretion of growth factors by stromal cells

Question 18

Describe bone marrow structure

Answer 18

1. Structure: reticular fibers, veins, arteries, sinusoids (type of capillaries), islands of cells
2. Red marrow: active hematopoiesis
3. Yellow marrow: fat, capillaries, retifular cells, inactive hematopoiesis

Question 19

What do growth factors regulate?

Answer 19

Regulate proliferation & maturation

Progenitor cells have surface receptors for specific cytokines and growth factors (glycoproteins)

Hematopoietic cells will die unless exposed to growth factors

Question 20

What are erythropoietins(EPO)?

Answer 20

Produced by kidneys increase erythrocyte precursors

Question 21

What are thrombopoietin (TPO)?

Answer 21

Hormone from liver stimulates thrombocytes formation

Question 22

What are cytokines?

Answer 22

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

Question 23

What is myelopoiesis?

Answer 23

Erythropoiesis
-formation of erythrocytes

Granulocytopouesis
-formation of granulocytes

Monocytopoiesis
-formation of monocytes

Thrombopoiiesis
-formation of thrombocytes(platelets)

Question 24

What is lymphopoiesis?

Answer 24

Formation of lymphocytes

Question 25

What simulates erythropoiesis ?

Answer 25

Erythrocyte formation, called erythropoiesis, occurs in adult red bone marrow of certain bones The main stimulates fir erythropoiesis is hypoxia Erythropoietin- produced by kidney

Question 26

Explain erythropoiesis

Answer 26

1. Proerythroblast 14- 19 um, no hemoglobin, large nucleus, basophilic cytoplasm 2. Basophilic (early) erythroblast: 12- 17 um, some hemoglobin, condensing nucleus 3. Polychromatophilic erythroblast: 12-15 um, “muddy” cytoplasm 4. Orthochromatophilic (late) erythroblast(normalblast): 8-12 um, increased hemoglobin 5. Reticulocyte: 7-8 um, no nucleus, sine ribosomes (blue with freshly blue stain)) 6. Erythrocyte: 7-8 um, only hemoglobin, no ribosomes

Question 27

Explain granolopoiesis (granulocytes formation)

Answer 27

1. Myoblasts: common precursor, 12-14 um, no granules, cytoplasmic blebs 2. Promyelocyte: 16-24 um, large nucleus, azurophilic granules (not specific) Nutrophils, eosinophils, or basophilic 3. Myelocyte: 10-12 um, condensed founded nucleus, specific granules 4. Metamyelocyte: kidney-shaped nucleus, specific granules 5. Band (stab): C-shaped nucleus, specific granules 6. Mature form: neutrophil, eosinophil, basophil

Question 28

How much granulocytes are formed in a day?

Answer 28

1. About 800,000 neutrophils, 170,000 eosinophils, 60,000 basophils per day 2. Controlled by cytokines, takes about 11 days

Question 29

Explain monocytopoiesis

Answer 29

Monocyte formation 1. Monoblasts: large, undifferentiated cells 2. Promonoblasts: 16-18 um, kidney shaped nucleus, azurophilic granules 3. Monocytes: “sky” blue cytoplasm, kidney shaped nucleus 4. Enter the circulation, proceed to tissue spaces, differentiate into macrophages

Question 30

Explain thrombopoietin (platelet formation)

Answer 30

1. Controlled by thrombopoietin 2. Megakaryoblast: 25:40 um, endomitosis, polyploid (about 32N) 3. Megakaryocyte: 40-100 um, large multi-lobed nucleus 4. Platelets are formed from fragments of megekaryote cytoplasm (1000’s per cell) 5. Platelet demarcation cells

Question 31

Explain lymphopoiesis

Answer 31

Lymphocyte formation 1. Colony forming units (CFU)- lymphocyte (B= bursa equivalent; T= thymus) 2. Lymphoblasts: large, undifferentiated cells 3. Prolymphocytes: medium-sized cells, condensing chromatin, no cell surface antigens 4. Some migrate from bone marrow to thymus, divide and differentiate to T-cells 5. Others remain in bone marrow, differentiate to B-cells , migrate to lymph tissues

Question 32

What adult stem cell plasticity?

Answer 32

Ability of stem cells to form specialized cell types of other tissues -useful for cell-based therapies

Question 33

What are the hematopoietic stem cells?

Answer 33

Neurons and glial stem cells Skeletal muscle cells Cardiac muscle cells Liver cells

Question 34

What are the bone marrow stromal cells?

Answer 34

Cardiac muscle cells Skeletal muscle cells

Question 35

What are the neural stem cells?

Answer 35

Blood cells Skeletal muscle cells

Question 35

What are the neural stem cells?

Answer 35

Blood cells Skeletal muscle cells