Differentiation
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| Differentiation | The process of transformation into a different cell type
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| Commitment | When the developmental fate of a cell becomes restricted, so that it will differentiate in a specific manner
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| Specification | 1st phase of commitment, fate still reversible; ex: ectodermal cell in medial region of trilaminar germ disc specified to develop into neural cell; if micromanipulator used to transfer it to lateral region of disc, it will differentiate into dermal cell
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| Determination | Final phase, when commitment becomes irreversible; commitment may occur before onset of differentiation; some cells are committed early in development, before there are any detectable changes in cell morphology or biochemistry
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| Autonomous specification | Intracellular signals (within cell) controlling cellular differentiation
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| Intercellular induction | Signals between cells controlling cellular differentiation
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| Hormones | Non-nutrient chemicals secreted by one cell to induce a response in another cell
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| Growth factors | Hormones that control cell cycle progression, cellular differentiation or morphogenesis during development
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| Differentiated cell types | Specialized cells within limited or no ability to transform into other cell types
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| Undifferentiated cell types | Cells that have not transformed into a specialized cell type
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| Specialized cell types | Cells with distinctive morphological characteristics and/or molecular processes
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| Generalized cell types | Cells lacking specialized characteristics
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| Totipotency | To have the potential to differentiate into any cell type and produce an entire organism (germ line, gametes, zygotes, and early blastomeres)
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| Pluripotency, multipotency | To have the potential to differentiate into multiple cell types (i.e. hemopoietic cells, fibroblasts)
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| Stem cells | Cells that differentiate into other cell types (i.e. spermatogonia, mesenchymal stem cells); either divide into more stem cells to propagate their own population or they differentiate when they divide
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| Progenitor (precursor) cells | Cells that must differentiate into other cell types and so cannot propagate their own poplation
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| Blastomere | Cells from cleavage stage embryos or blastocyts
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| Blast cell | Stem cells from any embryonic stage; usually named after cell types they produce; i.e. neuroblast (differentiates into neurons)
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| Mesenchyme | Loosely organized blast cells; usually thought of as mesodermal, but they may be derived from the other layers (e.g. ectodermal neural crest cells)
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| Metaplasia | Transformation of one differentiated cell type to another (i.e. smoking can induce pseudostratified epithelium of bronchi to become stratified squamous)
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| Dedifferentiation | To reverse the process of differentiation; for a specialized cell to transform into less specialized cell type
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| Anaplasia | Dedifferentiation to an embryonic cell type
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| Neoplasia | Abnormal, new growth (e.g. tumor formation); most neoplasias are anaplasias
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| Characteristics of differentiated cells | 1. specialized cellular structures and/or functions, 2. slow or arrested cell cycle progression, 3. impaired ability to transform into other cell types
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| Levels of differentiation | Differentiation is not an all-or-none process; some cells more differentiated than others; i.e. zygote = completely undifferentiated (will produce all cell types), hemopoietic cell = more differentiated (can only transform into blood cells)
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| Development and differentiation | process of development = progressive proliferation & differentiation of cells from zygote to adult; # of differentiated cells & degree of differentiation = increases throughout development; totipotent cells become pluripotent, end as differentiated cells
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| Regeneration and differentiation | differentiated cells lose ability to divide and proliferate; cannot proliferate = cannot replenish themselves after damage; highly differentiated cells (muscle, nerve) have little to no regenerative ability
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| Myogenesis | Muscle development; three classes of muslce (smooth, cardiac, skeletal)
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| Myoblasts | Muscle stem cells; myoblast formation is an example of determination; myoblasts will only form muscle
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| Muscle fibers | Muscle cells, often referred to as myocytes or myotubes; multiple myoblasts fuse together to form one large, syncytial skeletal muscle fiber; this is the completion of muscle differentiation
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| Earliest activators of myogenesis | Wnt (went) and Shh (sonic hedge hog); intecellular signaling molecules; secreted by neural cells in embryo
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| Pax-3 | Helix-turn-helix transcription factor that function as upstream activator of MyoD
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| Helix-loop-helix factors that induce skeletal myogenesis | Myf-5, Myf-6, Myo-D, myogenin; factors bind to each other's enhancers (activate each other's transcription)
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| Myf-6 | HLH; upstream activator of Myf-5
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| Myf-5 and Myo-D | HLH; Both contribute to differentiation of somites into myoblasts, although only one is required
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| Myogenin | HLH; Not required for myoblast formation, but is required for final differentiation into skeletal muscle fibers
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| Positive HLH's | Myf-5, Myf-6, MyoD, myogenin
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| Negative HLH's | Id
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| Ubiquitous HLH's | E2A
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| ___ ___ compete with ___ ___ for association with ___ ___ | Positive MyoD; negative Id; ubiquitous E2A
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| Why is Id negative? | Lacks DNA binding domain; prevents E2A from activating transcription
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| MyoD/E2A complex | Binds DNA sequence (E box - CannTG) found in promoters & enhancers of many genes required for myogenesis (ex: actins, myosins, troponin, creatine kinase, other HLH genes)
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| MEF-2 | Belong to MADS-box family of transcription factors; expression activated by MyoD and Myf-5; expression = binds HLH heterodimer to form trimeric complex
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| MEF-2 recognition sequence | CTAWWWWTAG (W = A or T); found adjacent to E boxes of many muscle specific promoters/enhancers; MEF-2 cooperates w/ HLH factors to activate muscle specific transcription
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