The Big Picture● What are cells?○ There are many ways to answer that■ Complex living systems■ Bats of protein that make more bags of proteins (e.g. ability to independently reproduce)● Prokaryotic do not have a nucleus whereas eukaryotic do● How do cells know what to do, where to go, etc.?○ Use stem cells as a model to discuss the answers to some of the questionsWhat is a stem cell?“Stem cells have the remarkable potential to develop into many different celltypes in the body during early life and growth. In addition, in many tissues that serve as a sort of internal repair system, dividing essentially w/o limit toreplenish other cells as long as the person/animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell, or become another type of cell with a more specialized function, such as muscle cells, a red blood cell, or a brain cell.”● A cell type in which its job is to divide to make more cells or differentiate into cells with specialized functions○ e.g. heart, blood, liver, etc.○ Yeast, amoeba are eukaryotic because they have a nucleus (single-celled organisms)Stem cellsCAN undergo cell divisionCan become many different types of cells (e.g. have the potential to differentiate into cells w/different functions)stem cells make more cellsdifferentiate into a specific cell typerepairsadult bodies contain stem cellscannot duplicate once it's a specified cell● terminally Differentiated cells○ Cannot undergo cell division○ Cannot differentiate any further○ perform spec. functions in the body e.g. muscle cells or neurons or bone cells○ does a specific function○ different cell types are different because they express different genes multipotent blood stem cell--> differentiation-->red blood celldifferentiated cells cannot duplicate because they don't receive signalsif they do-->cancer!stem cell to differentiated cell: fertilized egg-->fetushow does this happen? How do cells know which cell type to turn into?OUTSIDE OF CELlreceptor sits on cell surfaceO2, water, phospholipidsINSIDE OF CELLnote: make checklist of stem vs differentiated ● We can place stem cells into different categories depending on their differentiation potential, or their "potency"○ the potency of a cell specifies its differentiation potential, or potential to differentiate into diff cell types○ totipotency is the ability of a single cell to divide and produce All the differentiated cells in an organism including extra embryonic tissues○ pluripotent stem cells can give rise to any fetal or adult cell type. however, alone they cannot develop into a fetal or adult animal because they lack the potential to contribute to extra embryonic tissue , such as the placenta■ e.g. inner mass cells inside a blastocyst (week old fetus)○ multipotent progenitor cells have the potential to give rise to cells from multiple, but limited number of lineages○ unipotent are differentiated cells● Oct4: receptor to a stem cell● tumors are heterogeneous in a fetustotipotent: early embryopluripotent: inner cell mass stem cellzwhat's the same between stem cells and differentiated cells?their DNAFOR MOST STEM CELL TYPES: when differentiation occurs, the total DNA contentdoes not change.different types of stem cellsembryonic stem cells (ESC)E.G. inner cell mass of blastocystadult stem cellse.g. bone marrowneeded for tissue repairwhat are so,e other areas of the body where constant cell renewal is happening and where thee might be stem cells?induced pluripotent stem cells (iPS cells)induced pluripotent system cells are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state by being forced to express genes and factors important for,maintaining the defined properties of embryonic stem cellhave to kill embryonic stem cell in order to usenot hard to induce embryonic to be pluripotenthard to induce then to be liver cells real/hypothetical transduction pathwaysCell surface receptors (receiving physicals signalling componentKinasesPhosphatasestranscription factorsif stem cells and differentiated cells have the same Dna content then how do you get such diff types of cells with diff capabilities? gene expression● expression of diff genes leads to● diff proteins● diff receptors● diff function● All somatic cells have the SAME DNA○ But express different set of genes-->different cells○ differentiate or go through cell division● somatic cells=body cells not sex cells● All cells should have the same number of genes● every cell has the same genes no matter stem or differentiated● transcription: DNA (gene) -RNA polymerase-> mRNA (messenger)-ribosome-> protein● mRNA can only be expressed in genes with the DNA● stem cells only express oct4● cells receive an array of signals that tell them what to do○ survive○ grow and divide○ differentiate○ die-->apoptotic cell○ sometimes pathways get broken and cells that are told to die don't-->bad things○ necrosis: cells die and so do all the cells around them-->catastrophic● the same signal can be received by the same receptor but depending on the cell type, the signal may affect different outcomes● cytostolic signaling: need things to relay signal from molecules● effector molecules do other than gene expression● pathways contain multiple components● transcription factor screws gene expressions but not ion channel ○ cell yes signal○ receptor receives signal○ receptor activates protein kinases○ kinases activate transcription factors○ transcription factors mark genes for expression RTK pathway aka mapk pathwayHypothetical (simplified) Transduction Pathway● MAPK: Mitogen Activated Protein Kinase● Self Renewal Pathway activated by signal binding event○ Growth factor signals○ receptorRTK: Receptor Tyrosine Kinase○ Kinase domains phosphorylate each other (autophosphorylation)○ Phosphorylate take from Adenosine Triphosphate (ATP)-->stick onto a proteinr● Dimerization of receptor occurs upon signal binding● Phosphorylation: Change in the chemistry of a protein○ Turns on and off the protein● TFa not phosphorylated-->cannot go into the nucleus● Phosphorylation causes the chemistry of the molecule to change○ Activation, deactivation, differential binding characteristics, etc.■ Proteins structure = function○ Two types of kinase■ Serine■ Threonine● Signaling pathways can be regulated at every step●