分子细胞生物学：细生PBL

1、Stem CellTissue RenewalTissue Renewal-the inspiration of Blood&1.Stem Cell2.Tissue Renewal3.Inspiration of BloodKey TopicsStem CellStem cells are biological cells found in all multicellular organisms, that can divide (through mitosis) and differentiate into diverse specialized cell types, and ca

2、n self-renew to produce more stem cells. *In mammals, there are two broad types of stem cells1.embryonic stem cells, which are isolated from the inner cell mass of blastocysts Stem Cell-ClassificationStem cell -Classification2.somatic stem cells, which are found in various tissues. Tissue RenewalRen

3、ewal of damaged or dead cells in a manner which preserves tissue integrity help tissue maintenance. *In a developing embryo, stem cells can differentiate into all the specialized cellsectoderm, endoderm and mesodermbut also maintain the normal turnover of regenerative organs, such as blood, skin, or

4、 intestinal tissues. *In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. Why Blood Cells Need Renewal*Each type of blood cell finally died.Why Blood Cells Need Renewal-Cell cycle of blood cellsHuman erythrocytes are produced through a

5、 process named erythropoiesis, developing from committed stem cells to mature erythrocytes in about 7 days. When matured, in a healthy individual these cells live in blood circulation for about 100 to 120 days (and 80 to 90 days in a full term infant)1.ErythrocytesSome examplesWhy Blood Cells Need R

6、enewal*Platelets extruded from megakaryocytes*The average life span of circulating platelets is 8 to 9 days. Life span of individual platelets is controlled by the internal apoptotic regulating pathway, which has a Bcl-xL timer.*Old platelets are destroyed by phagocytosis in the spleen and liver.2.P

7、lateletsWhy Blood Cells Need RenewalThe average lifespan of (non-activated human) neutrophils in the circulation has been reported by different approaches to be between 5 and 90 hours. Upon activation, they marginate (position themselves adjacent to the blood vessel endothelium), and undergo selecti

8、n-dependent capture followed by integrin-dependent adhesion in most cases, after which they migrate into tissues, where they survive for 12 days.3.NeutrophilWhere are all kinds of blood cells from?Hematopoietic stem cells (HSCs) Hematopoietic stem cells (HSCs) are the blood cells that give rise to a

9、ll the other blood cells and are derived from mesoderm. They are located in the red bone marrow, which is contained in the core of most bones. Hematopoietic stem cells (HSCs) 1.Origin-variousIn mammalian embryology:firsrt detected in (day 2740) AGM (Aorta-Gonad-Mesonephros)then expand in fetal liver

10、colonize bone marrowalso found in umbilical cord bloodIn adults: in bone marrow, specially in the pelvis, femur and sternum. in peripheral blood in small numbers Hematopoietic stem cells (HSCs) The hematopoietic tissue contains cells with long-term and short-term regeneration capacities committed mu

11、ltipotent, oligopotent, and unipotent progenitors. HSCs constitute 1:10.000 of cells in myeloid tissue.2.CompositionHematopoietic stem cells (HSCs) They give rise to the myeloid lineages (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendriti

12、c cells) lymphoid lineages (T-cells, B-cells, NK-cells).3.DifferentiationHematopoietic stem cells (HSCs) Like all stem cells, HSCs can replenish all blood cell types (i.e. multipotent) and self-renew. A small number of HSCs can expand to generate a very large number of daughter HSCs. This phenomenon

13、 is used in bone marrow transplantation, when a small number of HSCs reconstitute the hematopoietic system. This process indicates that, subsequent to bone marrow transplantation, symmetrical cell divisions into two daughter HSCs must occur.4.FunctionHematopoietic stem cells (HSCs) *Blood Platelet(P

14、LT) have no cell nucleus; they are fragments of cytoplasm which are derived from the megakaryocytes of the bone marrow, and then enter the circulation.*The main function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site of interrupted endothelium. They gather

15、at the site and unless the interruption is physically too large, they plug the hole. 5.ExampleHematopoietic stem cells (HSCs) 5.ExampleHematopoietic stem cells (HSCs) 5.Example(1) Megakaryocytes are derived from hematopoietic stem cell precursor cells in the bone marrow. They are produced primarily

16、by the liver, kidney, spleen, and bone marrow. These multipotent stem cells live in the marrow sinusoids and are capable of producing all types of blood cells depending on the signals they receive. (2) The primary signal for megakaryocyte production is thrombopoietin血小板生成素or TPO. TPO is sufficient b

17、ut not absolutely necessary for inducing differentiation of progenitor cells in the bone marrow towards a final megakaryocyte phenotype. Other molecular signals for megakaryocyte differentiation include GM-CSF, IL-3, IL-6, IL-11, chemokines (SDF-1, FGF-4). and erythropoietin. (3)The megakaryocyte de

18、velops through the following lineage: CFU-Megmegakaryoblastpromegakaryocytemegakaryocyte.Ps:CFU-Me: pluripotential hemopoietic stem cell or hemocytoblastHematopoietic stem cells (HSCs) *So HSCs need continuously differentiation and replication to produce terminally differentiated cells and self clon

19、al cells. *This phenomenon is also seen happening in other tissues of human body, though through a little different pathways!Clinical CorrelationSince hematopoietic stem cells can differentiate into blood cells that belongs to the systemic circulation, they are an ideal target cell for gene therapy,

20、 which is why most gene therapy projects list hematopoeitic stem cells as the main study. Now, the hematopoeitic stem cell has become the stem cell people understand and use the most.Radiotherapy and chemotherapy are the two major clinical treatments for malignant hematologic diseases.By the 80s bone marrow transplant has