Stem Cells Flashcards
4 characteristics of stem cells
- remain in undifferentiated state
- can make another stem cell and also a new cell that is committed to differentiation when they divide
- they can undergo an unlimited number of cell divisions
- have potency
what is a totipotent stem cell
ability to produce all of the differentiated cells in an organism, including embryonic tissues (placenta)
what is a pluripotent stem cell
cell that can give rise to any fetal or adult cell type except extra-embryonic tissues (no placenta)
what is a multipotent stem cell
cell that can giverise to multiple lineages
what is a unipotent stem cell
can only give rise to one type of undifferentiated cell
what is the concept of asymmetric stem cell division
each newly formed daughter cell has a different fate, stem cell plus a future differentiation cell
what is environmental asymmetry
daughter cells produced by division of stem cell are initially the same, but environmental influences direct one daughter cell to differentiate
what is divisional asymmetry
internal factors direct one of the daughter cells to follow a path of differentiation
1st step in differentiation
transit amplifying cell is developed, which divides frequently but for a limited amount of divisions, resulting in the amplification of resulting differentiated cell population
what are transit amplifying cells
the first step after a cell has decided that it will differentiate, divides frequently, amplification of resulting differentiated cells
significance of progeny of transit amplifying cells
can differentiate in response to environmental cues (extracellular signaling)
what is the impact of extracellular matrix on differentiation
physical properties of ECM can determine what type of cell that bone marrow stromal cells can differentiate to
what are bone marrow stromal cells
cell found in bone marrow that can differentiate into fat cells, cartilage, or bone cells
what do bone marrow stromal cells develop to on stiff matrix and how?
bone cell
because there is a strong adhesion between the cell and the ECM, causes transcription factors YAP and TAZ to become active
what do bone marrow stromal cells develop to on soft matrix and how?
fat cell
because there is weak adhesion between cell and ECM, YAP and TAZ remain off
what 5 genes are highly expressed in pluripotent stem cells?
- Klf4
- Lin28
- Oct4
- Nanog
- Sox2
what are the molecular markers of cell differentiation
each stage of differentiation is characterized by a different pattern of gene expression
where are somatic stem cells found in adults?
niches
what tissues have stem cell niches
SHENG
- skeletal muscle
- hematopoeitic tissue
- epidermis
- neural tissue
- gut epithelium
what type of stem cells are the stem cells in the niche tissue?
multipotent
where are stem cells found in the epidermis/glabrous skin?
near tips of dermal papillae in epidermis, in the bulge region of hair follicles
what can skin stem cells differentiate into?
keratinocytes, sebaceous gland cells, hair cells
how are stem cells distinguished from other cell types in the skin?
- the stem cells express high levels of beta1 integrin
- differentiating cells express keratin-10
- transit amplifying cells marked by BrdU incorporation
what do differentiating skin cells express?
keratin-10
what do skin stem cells express that distinguish them from other cells
beta1 integrin
what do skin transit amplifying cells express
marked with BrdU incorporation
where are gut epithelium stem cell niches found
crypts in the bottom of pockets along the intestinal wall
what can gut epithelium stem cells differentiate into?
absorptive cells (enterocytes), goblet cells, enteroendocrine cells, paneth cells
what occurs once the gut stem cells are differentiated?
the cells slide along epithelium upward to cover villus
what type of signaling is utilized in the gut epithelium to control stem cell differentiation?
wnt signaling leads to the expression of notch and delta.
explain the use of notch and delta in the gut epithelia
paneth cells in the crypt express delta, which activates notch signaling in the stem cells, preventing them from differentiating (lateral inhibition)
what are paneth cells?
nondividing terminally differentiated secretory cells
what role does notch play in the transit amplifying cells in the gut epithelia?
notch signaling maintains proliferative state in transit amplifying cells which ultimately give rise to the absorptive cells of the villi
what role does delta play during differentiation?
expression causes some cells to differentiate into secretory cells
where are neural stem cell niches found
subventricular zone of lateral ventricle, hippocampus
what do neural stem cells differentiate into
neurons, glial cells (astrocytes, oligodendrocytes)
in humans what is the purpose of neural stem cells in the hippocampus?
providing new neurons needed for constant turnover of cells in this region
in mice, purpose of neural stem cells in the ventricles?
these stem cells constantly produce progenitor cells, that migrate to the olfactory bulb, where they differentiate into neurons to replace the ones constantly lost
what are the skeletal muscle stem cells
satellite cells (myosatellite cells)
where are satellite cells found
between sarcolemma of skeletal muscle fibers and the surrounding basal lamina
what do the satellite cells do in the muscles
lay in quiescent state until muscle damage induces them to re-enter the cell cycle and produce progenitor cells
what happens when satellinte cells are activated
express high levels of myoD that results in differentiation into myoblasts and ultimately formation of new myofibers
where are hematopoietic stem cells found
bone marrow
what are HSC
hematopoietic stem cells capable of indefinite self renewal and gives rise to multipotent progeniors
what are MPP
multipotent progenitors that are differentiated from HSC
what is the CMP
common myeloid precursor, derived from the multipotent hematopoietic progenitor, gives rise to GMP and MEP
what is GMP
granulocyte/macrophage progenitor
what is MEP
megakaryocyte/erythrocyte progenitor
what is a “-blast”
cell that has the ability to divide and proliferate, and is the precursor to a fully differentiated cell
A TRANSIT AMPLIFYING CELL!!!
what is the CLP
common lymphoid progenitor, derived from the multipotent hematopoietic progenitor, gives rise to pro B cells and NK/T cells
what do proB cells give rise to
pre-B cells which give rise to B cells
what do NK/T cells give rise to
T cells and NK cells
how are hematopoietic cells identified?
presence of specific proteins found on the outer surface of their plasma membranes
what do HSC’s express?
KIT, SCA1 and low levels of CD34 and FLK2
how do the stem cell niches maintain their niches?
communication between stem cells and supporting cells within their niches
example of niche maintenance
hematopoietic stem cells must remain in contact with stromal cells within bone marrow to retain stem-ness
HSC niche maintenance process
- stem cells express KIT receptors on their cell surface, which binds to Kit ligand expressed on surface of stromal cells
- kit receptor/ligand binding initiates signaling cascade within stem cell that allows the cell to remain stem cell
- when stem cell divides, interaction of stromal cells is lost in one of the cells, therefore Kit receptor is no longer active and the cell is committed to differentiation
what occurs when an HSC divides in terms of maintenance
interaction of stromal cells is lost in one of the cells, and kit receptor is no longer active. the cell is committed to differentiation
what tissues are devoid of stem cells
auditory epithelium, retinal epithelium
is terminal differentiation really terminal?
no, in certain conditions terminally differentiated cell can be converted back into pluripotency
what is a somatic cell nuclear transfer ? (SCNT)
cloning technique where nucleus of terminally differentiated somatic cell is transferred into the cytoplasm of an enucleated egg
product of SCNT
reproductive and therapeutic cloning (potential for immunological rejection minimized
where are embryonic stem cells?
derived from inner cell mass of a blastocyst and are pluripotent
what is iPS cells
induced pluripotent stem cells, terminally differentiated somatic cells (fibroblasts) that are collected from an individual and expressed with oct3/4 and Klf4, which causes the differentiated cell to revert back to a pluripotent, undifferentiated stem cell state, which then can be forced to differentiate into any cell type
what is the major difference ethically between SCNT and iPS
iPS does not involve the creation and destruction of a human embryo
which genes are the master regulators of induced pluripotency
- Klf4
- oct4
- Nanog
- sox2
why are the KONS master regulators?
induce their own expression and also induce the expression of each other, generating a self sustaining feedback loop that mainains a stem cell like state
1st wave of iPS regrogramming
cellular proliferation, metabolism, cytoskeletal organization genes are expressed and genes associated with fibroblast development are repressed
2nd wave of iPS reprogramming
genes required for embryonic development and stem cell maintenance are induced
potential uses for iPS?
- analyze genetic disease mechanism or for discovery of therapeutic drugs
- repair genetic defect by being induced to differentiate in vitro and grafted back into the patient without initiating an immune response
what do erythroblasts give rise to
erythrocytes
what do megakaryoblasts give rise to
megakaryocytes, platelets
what do monoblasts give rise to
monocytes, then macrophages
what do myeloblasts give rise to
neutrophils
what do eosinophiloblasts give rise to
eosinophils
what do basophiloblasts give rise to
basophils
