MCB 2210 001 4 22 2015 Stem Cells Human development begins when a sperm fertilizes an egg and creates a single totipotent cell zygote o Totipotency ability of a sinlge cell to divide and produce all the differentiated cells in a organism including extra embryonic tissue o In the first hours after fertilization this cell divides into identical totipotent cells which can later develop into any of the three germ layers of a human and into cells of the placenta Endoderm inner layer Mesoderm middle layer Ectoderm outer layer Somatic cell any cell that forms the body of a multicellular organism o Any cell other than a gamete germ cell or stem cell Gametes cells that fuse during sexual reproduction Germ cells give rise to gametes Differentiation process by which a less specialized cell becomes a morespecialized cell type o All cells of an organism contain the same DNA yet cells can be very different o In any given cell some genes are turned on and some are turned off Some expressed at high levels some low Differential gene expression basis of differentiation of multiple cell types during development o Depending on which genes are being transcribed the transcriptome and translated a cell will express a particular suite of proteins proteome o Some cellular responses may act through the existing proteins of a cell Some may lead to changes in gene expression that change the suite of proteins in the cell o Transcription factors proteins that bind DNA and can activate or repress the transcription of other genes Often targets of signal transduction pathways Can develop complex gene regulatory networks o Combo of signal transduction and transcription coordinates the differentiation and behavior of cells in a developing organism o In other situations the DNA and its associated histone proteins can become chemically modified methylation or acetylation causing the underlying genes to be held in a transcriptionally active or inactive semi permanent state Sometimes these modifications can be stably inherited from one cell to another epigenetics Stem Cells undifferentiated cells that can reproduce themselves and also give rise to diverse specialized cell types o Pluripotent stem cells can differentiate into any adult cell type They cannot develop into an animal because they lack the potential to form a placenta o Multipotent stem cells can give rise to cells from a limited number of lineages Terminally differentiated cells cells that are considered to be permanently committed to a specific function Stem cells characterized by the property of self renewal and the capacity for differentiation o Provide an indefinite supply of fresh differentiated cells where these are lost discarded or needed in greater numbers o Defining properties It is no itself terminally differentiated It can divide without limit When it divides each daughter has two possible fates Can remain a stem cells Can embark on a course that commits it to terminal differentiation C elegans is an important model organism for studying cell lineage differentiation and death o Nematode o Transparency facilitates the study of cellular functions o The developmental fate of every single somatic cell has been mapped out These patterns of cell lineage are largely invariant between individuals In mammals cell development from the embryo is more largely dependent on cellular cues A large number of addition cells are eliminated by programmed cell death apoptosis o Regulation by small RNAs appears to play a role in controlling pluripotency development programmed cell death and many other things Mammalian embryonic stem ES cells can be cultured and differentiated in vitro o Adults have many populations of stem cells Some human stem cells function in skin renewal o Epidermis epithelial tissue forms the outer covering of the skin and creates a waterproof barrier that s self repairing and continually renewed Beneath this lies a relatively thick layer of connective tissue Tough collagen rich dermis Beneath that is an underlying fatty subcutaneous layer or hypodermis Fundamental component of the skin o Humans renew the outer layers of their epidermis thousands of times in a lifetime o Basal layer of epidermis contains some cells that remain undifferentiated and carry on dividing for this whole period continually throwing off descendants that commit to differentiation leave the basal layer and eventually get discarded The process can be maintained only if the basal cell population is self renewing o The epidermis must therefore contain some cells that generate a mix of progeny including daughters that remain undifferentiated and some that differentiate o Stem cells required wherever there s recurring need to replace differentiated cells that can t themselves divide Clustered near the tips of the dermal papillae Divide infrequently giving rise via a sideways movement to transit amplifying cells which occupy the intervening regions Transit amplifying cells divide frequently but for a limited number of division cycles at which they begin to differentiate and slip out of the basal layer The precise distribution of stem cells and transit amplifying cells varies from one region of the epidermis to another Human Stem Cells HSCs found in bone marrow peripheral blood and umbilical cord blood o Bone marrow transplantation BMT and peripheral blood stem cell transplantation PBSCT procedures that restore stem cells that have been destroyed by high doses of chemotherapy and or radiation therapy Most commonly used in treatment of leukemia and lymphoma Autologous transplants patients receive their own stem cells Allogeneic transplants patients receive stem cells from their brother sister or parent A donor not related to patient may be used Specialized cells are formed by a one way process and they become increasingly committed to their fate o Certain experimental procedures enable a cells to change into a different kind Nuclear reprograming a switch in nuclear gene expression from kind of somatic cell to that of an embryonic or other cell type Mammalian somatic cell nuclear transfer Induction of pluripotency by ectopic gene expression Its possible to derive one kind of specialized cells from another from the SAME INDIVIDUAL o Identifying how reprogramming takes place can help us understand how cell differentiation and specialized gene expression are normally maintained o Nuclear reprogramming enables the culture of cell lines from diseased tissues and allows us to analyze