LW_BCH4122_Lecture5_2009Sep-1

LW_BCH4122_Lecture5_2009Sep-1 - 9/23/2009 1 Lecture 5....

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Unformatted text preview: 9/23/2009 1 Lecture 5. Adult stem cells (continue) and Application Embryonic hematopoiesis (continue) Application of adult stem cells HSC Disorders of hematopoiesis Application of HSC MSC Neural stem/progenitor cells Cardiac progenitors (Source of image: ht p://www.paterson.man.ac.uk/images/groups/scbio1.jpg) (Aorta- Gonado- Mesonephros) Embryonic Hematopoiesis Mouse The latest findings regarding the source of HSC during mouse embryonic development Embryonic Hematopoiesis Nature 446, 996 - 997 (2007). Previous theory Current theory 9/23/2009 2 Summary of Embryonic hematopoiesis - Mouse Previous theory: The yolk-sac-derived, primitive blood-forming cells are transient and die; all the adult HSC (blood-forming cells) originate from the AGM around E10.5. Current theory: at least some adult HSCs come from the yolk sac (contrary to the view that yolk-sac and intra-embryonic haematopoiesis are completely separated in mammals) Embryonic Hematopoiesis Nature 446, 996 - 997 (2007). & Nature 446, 1056 1061 (2007 Embryonic hematopoiesis limited studies using human embryo Limited research with human embryos has shown that human hematopoie tic cell clusters arise from the AGM region between the 27th and 40th day of human development, through an intermediate blood-forming endothelium stage Embryonic Hematopoiesis Developm ent 1999;126: 793-803; Blood 1996; 87: 67-72. Im m unity 2001; 15: 487-495 Embryonic Hematopoiesis Embryonic hematopoiesis studies using human embryonic stem cells 9/23/2009 3 Embryonic Hematopoiesis Embryonic hematopoiesis studies using human embryonic stem cells Lecture 5. Adult stem cells (continue) and Application Embryonic hematopoiesis (continue) Application of adult stem cells HSC Disorders of hematopoiesis Application of HSC MSC Neural stem/progenitor cells Cardiac progenitors 1. Polycythemia Vera (PV): Excessive production of mature red cells (sometimes also platelets and granulocytes). It may lead to, among other things, increased blood viscosity, headaches, strokes and myocardial infarcts 2. Essential Thrombocytosis (ET): Overproduction of abnormal platelets resulting in bleeding and thrombosis Both diseases are caused by V617F mutation in the JAK2 protein involved in EPO and TPO signaling, which results in its constitutive activation Hematological diseases associated with abnormal hematopoiesis Disorders of Hematopoiesis 9/23/2009 4 Hematological diseases associated with abnormal hematopoiesis 3. Chronic Myelogenous Leukemia (CML): Dysregulated proliferation of a single HSC and its progeny leading to excessive production of relatively normal granulocytes. Caused by 9:22 translocation leading to bcr-abl fusion (so-called Ph 1 chromosome) Im ages from W ikipedia.org Philadelphia chrom osom e Used w ith permission under G NU Free Documentation License Disorders of Hematopoiesis 4. Acute Myeloid Leukemia (AML): Increased numbers of myeloblasts (granulocyte precursors) in the BM and blood. precursors) in the BM and blood....
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LW_BCH4122_Lecture5_2009Sep-1 - 9/23/2009 1 Lecture 5....

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