Stem Cells Last class Cytoskeletal func ons in many di erent cell types Fibroblasts migra on ac n Osteoblasts collagen secre on Neuronal cells growth cone ac n MTs axonal tra cking MTs motors and exocytosis ac n Muscle cells sarcomeres and contrac on ac n myosin Macrophages extravasa on ac n phagocytosis ac n podosome assembly ac n T cells B cells An gen presen ng cells immunological synapses ac n Respiratory epithelia Sperm mo le cilia agella MTs motors Sensory cells non mo le cilia primary cilia MTs motors MANY other cells Figure 23 52 Molecular Biology of the Cell Today How is this cell diversity generated A to potent zygote pluripotent stem cells and cell di eren a on Human development begins when a sperm fer lizes an egg and creates a single to potent cell zygote To potency is the ability of a single cell to divide and produce all the di eren ated cells in an organism including extra embryonic ssues In the rst hours aIer fer liza on this cell divides into iden cal to potent cells which can later develop into any of the three germ layers of a human endoderm inner layer mesoderm middle layer or ectoderm outer layer and into cells of the placenta A soma c cell is any cell that forms the body of a mul cellular organism any cell other than a gamete germ cell or stem cell By contrast gametes are cells that fuse during sexual reproduc on and germ cells are cells that give rise to gametes Di eren a on is the process by which a less specialized cell becomes a morespecialized cell type Stem cells are undi eren ated cells that can reproduce themselves and also give rise to diverse specialized cell types Pluripotent stem cells can di eren ate into to any adult cell type They cannot develop into an animal because they lack the poten al to form a placenta Mul potent stem cells can give rise to cells from a limited number of lineages e g a hematopoie c stem cell is a blood stem cell that can develop into several types of blood cells but not brain cells or other types of cells Terminally di eren ated cells are cells that are considered to be permanently commiPed to a speci c func on Important vocabulary ES cells HSCs Some skin cells Liver hepatocytes but self renew Jaenisch 2008 Di eren a on Review from Course Introduc on All cells of an organism contain the same DNA yet our cells can be drama cally di erent Remember a cell whether a single celled organism or a cell in a mul cellular organism does not express all of its genes all of the me In any given cell some genes are turned on some are turned o Some are expressed at high levels some low This is known as di eren al gene expression and is the basis of the di eren a on of mul ple cell types during development Depending on which genes are being transcribed the transcriptome and translated a cell will express a par cular suite of proteins the proteome One of the central goals of cell biology is to understand how all those proteins interact with themselves and with other cellular components to carry out specialized cell func ons and to respond to changes inside or outside of the cell Sensing changes or s muli communica ng them through the cell and responding is the process of signal transduc on Di eren a on Review from Course Introduc on Some cellular responses may act through the exis ng proteins of a cell Some may lead to changes in gene expression that change the suite of proteins in the cell Transcrip on factors are proteins that bind DNA and can ac vate or repress the transcrip on of other genes and they are oIen targets of signal transduc on pathways Since transcrip on factors can also regulate the expression of other transcrip on factors cells can develop complex gene regulatory networks This combina on of signaling and transcrip onal regula on coordinates the di eren a on and behavior of cells in a developing organism In addi on the DNA and its associated histone proteins can become chemically modi ed i e by methyla on or acetyla on causing the underlying genes to be held in a transcrip onally ac ve or inac ve semi permanent state Some mes these modi ca ons can be stably inherited from one cell to another Such changes in the gene c poten al of a cell without changes to the underlying DNA sequence are the topic of epigene cs The accumula on of epigene c marks also plays an important role in the di eren a on of cells and the restric on of cell fates Stem Cell Biology is greatly informed by and greatly informs our understanding of cellular di eren a on mechanisms and the elds of Developmental Biology and Gene cs Stem cells give rise to di erent cell types Stem cells are characterized by the property of self renewal and the capacity for di eren a on They provide an inde nite supply of fresh di eren ated cells where these are lost discarded or needed in greater numbers The de ning proper es of a stem cell are as follows 1 It is not itself terminally di eren ated i e not at the end of a pathway of di eren a on 2 It can divide without limit or at least for the life me of the animal 3 When it divides each daughter has two possible fates it can either remain a stem cell or it can embark on a course that commits it to terminal di eren a on external cues Figure 23 5 Molecular Biology of the Cell internal cues Figure 23 6 Molecular Biology of the Cell C elegans is an important model organism for studying cell lineage di eren a on and death Research on the nematode worm Caenorhabdi1s elegans C elegans has provided many insights into the mechanisms by which gene expression controls pluripotency di eren a on development and death A cellular family tree C elegans as a model organism C elegans was the rst mul cellular organism to have its genome completely sequenced 1998 Its transparency facilitates the study of cellular di eren a on and other developmental processes in the intact organism The developmental fate of every single soma c cell 959 in the adult hermaphrodite 1031 in the adult male has been mapped out These paPerns of cell lineage are largely invariant between individuals in contrast to mammals where cell development from the embryo is more largely dependent on cellular cues In both sexes a large number of addi onal cells are eliminated by programmed cell death We will discuss programmed cell death apoptosis in our nal lecture Visualizing C elegans development MCB Figure 21 5 In 2002 the Nobel Prize in Physiology or Medicine was awarded to Sydney Brenner Robert Horvitz and John Sulston for their work on the gene cs of organ development