FORM & FUNCTION (Stem Cells) Flashcards
Ectoderm eventually becomes
-outer surface
-CNS
-neural crest
Mesoderm eventually becomes:
-dorsal
-paraxial
-intermediate
-lateral
-head
Endoderm eventually becomes:
-digestive tube
-pharynx
-respiratory tube
Germ cells become:
-male: sperm
-female: egg
Main cellular processes that are key to successful development are:
- Cell proliferation
- Differentiation
- Morphological Changes and Cell migration
- Apoptosis
*elicited and/or regulated by factors
Cell proliferation:
-an increase in cell number due to mitosis
Differentiation:
-a gradual process by which specialized cell types develop from a pool of cells
Apoptosis:
-programmed cell death
-mediated via enzymes including caspases and DNases
What are the additional key decisive factors/processes in embryonic development?
-cell-to-cell communication
-signaling pathways
-induction and competence
-adhesion and migration
-morphogens
-genes
-transcription factors
Signaling pathways:
-11 main ones involved in development
-each signal is transmitted in a LINEAR MANNER and act on a single response element in target genes
-specific patterns of signaling for a given species
-changes elicited by these signals during development are IRREVERSIBLE
Examples of signalling pathways involved in development:
-Notch
-Wingless (Wnt)
-transforming growth factor (TGF-beta)
-fibroblast growth factor (Fgf)
Induction:
-process by which a particular group of cells influences the fate of an adjacent group of cells
-generally mediated via paracrine or contact-dependent signaling
Competence:
-refers to ability of a cell to respond to an inductive signal
-competent cell must express the receptors for the inducer(s)
Ex. response of a group of cells to a transcription factor
Cell adhesion is mediated by:
-cadherins and integrins
Cadherins in one cell:
-interact with cadherins in adjacent cells
Adherins:
-help with the adhesion of cells to various ligands
Heavy cell migration during development:
-cells use different forms of movement for migration depending on the stage of development
What are determinants of cell migration?
-molecular composition of the ECM and matrix architecture of cells
Morphogens:
-a substance that can determine the fate of a cell/cell’s differentiation by way of its presence in the cellular microenvironment
-effects are CONCENTRATION dependent
-elicit stimulatory or inhibitory effects
Example of a morphogen:
-signaling molecules, sonic hedgehog (Shh) is important for formation of spinal cord
Effects of Shh are dependant on:
-its concentration
-duration of exposure
-interaction with other target genes and/or signals/pathways
Chromatin:
-DNA and protein
*structure has a heavy influence on gene expression
Epigenome:
-a determinant of how cells remember their identity
-comprises of processes and signals
Epigenome comprises of processes and signals examples:
-DNA methylation
-histone modification
-other factors including small RNAs
Transcription factors:
-proteins that can bind to the enhance or promoter regions of the DNA to up- or down-regulate the gene transcription to form mRNAs
*very diverse
Examples of transcription factors:
-Sry,Sox: sex determination
-Hox: regional identity
-Mef-2: muscle development
-Pax: eye development
-Oct-4: pluripotency
-Tbx: limb development
Stem cells:
-specialized cells able to undergo self-renewal and produce daughter cells that possess the same features of the cells from which they originally derived
-from cell lineages play a key role in forming tissues and organs
-classified based on ‘potency’ and its occurrence during development/life
Stem cell classification based on potency:
-totipotent (ex. embryonic cells)
-pluripotent
-multipotent (ex. mesoderm, endoderm, ectoderm)
-unipotent
-progenitor cells
Stem cell classification based on occurrence during developing/life:
-embryonic stem cells
-adult stem cells
Totipotent:
-develops from the inner cell mass in the developing embryo
-can develop into any cell type in the embryo, including trophoblastic placental cells
*most potent
Pluripotent:
-arise from the embryonic cells
-can differentiate into any cells within the embryo, except trophoblastic placental cells
Multipotent:
-derived from embryonic cells, but have limited linage capabilities
Unipotent:
-cells are destined to become a specific cell type after a limited number of divisions
Progenitor cells:
-more differentiated than stem cells and have limited self-renewal capability
Terminal differentiation is when:
-cells within specific lineage reaches a mature stage, where further differentiation or division does not occur
Embryonic stem cells:
-stems cells in embryo
-originating from the inner cell mass and those that are from multiple lineages
-contribute to embryonic development, including the formation of primary germ layers
Adult stem cells:
-resident stem cells within adult tissues and organs
-enable tissue self-renewal and repair
-help maintain tissue integrity and function, especially when adverse events (ex. infection, trauma, degenerative changes) occur
Ex. bone marrow, intestinal crypts
Intestinal crypts:
-crypt base columnar stem cells give rise to all the cells especially the enterocytes
>become proliferating transit-amplifying cells (move from base to the tip
>become enterocytes at top=absorb nutrients
Induced pluripotent stem cells (iPSCs):
-somatic cells could be reprogrammed to develop cells of specific lineage by introducing specific TFs and by providing the supportive milieu for the cells to differentiate and grow
>make them become ectoderm, mesoderm and endoderm
TFs (iPSCs):
-introduction of TFs=transfection
-cause nuclear reprogramming in fully differentiated adult cells
Transfection TF examples:
Combination of: (Yamanaka factors)
-Sox-2
-Oct-4
-c-Myc
-Klf-4
Growth factors (iPSCs):
Ex. TGF-beta
-provided in the media are critical in determining the lineage of stem cells
-choosing the right mix of growth media=can develop cells within specified lineages
Potential applications if iPSCs in vet med:
-take any animal’s differentiated cells and get iPSC
-then do a transplant of them when they have differentiated again (osteocyte, adipocyte, chondrocytes, neural cells)
