Molecular Fundamental - Stem Cells & Cellular Differentiation

stem cells remain in what state?

undifferentiated state

when stem cells divide, what can they do?

either make another stem cell or produce a new cell that is committed to differentiation

stem cells have potency, which is what?

stem cell’s potential to differentiate into different cell types

what does totipotent mean?

cell that has the ability to produce all of the differentiated cells in an organism, including extra-embryonic tissue (placenta)

what does pluripotent mean?

cell that can give rise to any fetal or adult cell type except those of extra-embryonic tissue

what does multipotent mean?

cell that can give rise to multiple lineages

what does unipotent mean?

cell that can give rise to only one type of differentiated cell

stem cells can divide in an asymmetric fashion, which means what?

each newly formed daughter cell has a different fate

what are the two types of asymmetrical division that stem cells can undergo?

• environmental asymmetry

• divisional asymmetry

what does environmental asymmetry mean?

daughter cells produced by the division of a stem cell are initially the same, but environmental influences direct one daughter cell to differentiate

what does divisional asymmetry mean?

internal factors direct one of the daughter cells to follow a path of differentiation

what is the first step of differentiation?

transit amplifying cells

the division of amplifying cells results in what?

the “amplification” of the resulting differentiated cell population

the progeny of transit amplifying cells can differentiate in response to what?

environmental cues (extracellular signaling molecules for example)

bone marrow stromal cells are a type of cell found in bone marrow that have the ability to do what?

differentiate into fat cells, cartilage cells, or bone cells

what can determine what type of cell bone marrow stromal cells differentiate into?

the physical properties of the extracellular matrix

a stiff matrix causes the transcription factors YAP and TAZ to do what?

become active

if YAP and TAZ are active, what cells form?

bone cells

a soft matrix causes the transcription factors YAP and TAZ to do what?

remain off

if YAP and TAZ remain off, the cell differentiates into what?

fat cell

pluripotent stem cells have four genes that are highly expressed. what happens as the cells commit to a more differentiated lineage?

they turn off these genes and begin to express other genes that are more specific to that particular tissue

where are stem cells found in adults?

in niches

what are niches?

specific regions (microenvironment) in adult tissue where the tissue’s stem cells reside

what tissues have stem cell niches?

• epidermis

• gut epithelium 

• neural tissue

• skeletal muscle 

• hematopoietic tissue

cells in the stem cell niche of adult tissues are what?

multipotent

what describes the stem cell niches of skin?

in glabrous skin, they are found near the tips of the dermal papillae in the epidermis

what can skin stem cells differentiate into?

• keratinocytes

• sebaceous gland cells

• hair cells

skin stem cells express high levels of what?

β1 integrin

differentiating skin cells express what?

keratin-10

what describes gut epithelium stem cell niche?

stem cells are found in structures call crypts (bottom of pockets along intestinal wall)

gut epithelium cells can differentiate into what?

• absorptive cells (enterocytes)

• goblet cells

• enteroendocrine cells

• paneth cells

what are neural stem cell niches?

• subventricular zone of the lateral ventricle

• hippocampus

what can neural stem cells differentiate into?

• neurons

• glial cells (astrocytes and oligodendrocytes)

satellite cells (myosatellite cells) are also what?

skeletal muscle stem cells

where are skeletal muscle cells located?

between sarcolemma of skeletal muscle fibers and the surrounding basal lamina

skeletal muscle stem cells lay in a quiescent state until what?

a stimulus (muscle damage) induces them to re-enter the cell cycle and produce progenitor cells

when skeletal muscle cells are activated, they express high levels of what that results in what?

transcription factor MyoD that results in differentiation into myoblasts and ultimately formation of new myofibers

what is the hematopoietic stem cell niche?

bone marrow

the hemotopoietic lineage is what?

the most diverse and best characterize stem cell lineage of the body

the common myeloid progenitor (CMP) gives rise to what?

GMP (granulocyte/macrophage progenitor) and MEP (megakaryocyte/erythrocyte progenitor)

communication between stem cells and supporting cells within the niche is important for what?

stem cell maintenance

hematopoietic stem cells must remain in contact with ______ ________ within the bone marrow in order to remain their stem-ness.

stromal cells

how do hematopoietic stem cells remain in contact with stromal cells?

through the kit receptors on the stem cell surface and the kit ligand expressed on the surface of stromal cells

what are the types of tissues without stem cells?

• auditory epithelium

• retinal epithelium 

damage to cells in tissues without stem cells results in what?

permanent loss of that tissue’s function

under certain conditions, a terminally differentiated cell can do what?

be converted back to a state of pluripotency (stem cell)

what ways can a terminally differentiated cell be converted back to a state of pluripotency?

• somatic cell nuclear transfer (SCNT)

• induced Pluripotent Stem (iPS) cells

embryonic stem cells (ES) are derived from what?

inner cell mass of a blastocyst

embryonic stem cells are what?

pluripotent

what describes somatic cell nuclear transfer (SCNT)?

cloning technique in which the nucleus of a terminally differentiated somatic cell is transferred to the cytoplasm of an enucleated egg

in reproductive cloning, a new multicellular organism is produced from a single parent and is what?

genetically identical to the parent

therapeutic cloning generates what?

personalized embryonic stem cells

with therapeutic cloning, what is minimized?

potential for immunological rejection

why do ethical issues have to be considered with somatic cell nuclear transfer?

because it requires the destruction of a human embryo

what is an example of reproductive cloning?

Dolly the Sheep

with iPS cells, a combination of three key genes are expressed in the somatic cells in vitro causing what?

the differentiated cell to revert back to a pluripotent, undifferentiated (stem cell) state

what is the first wave of new gene transcription that occurs during iPS cell reprogamming?

• cellular proliferation, metabolism, and cytoskeletal organization genes are expressed

• genes associated with fibroblast development are repressed

what is the second wave of new gene transcription that occurs during iPS cell reprogamming?

genes required for embryonic development and stem cell maintenance are induced

iPS cells generated from a patient with a genetic disease can be used to do what?

analyze the disease mechanism or for discovery of therapeutic drugs

iPS cells can also be used to do what?

repair a genetic defect by being induced to differentiated in vitro and grafted back into the patient without initiating an immune response

the iPS cell can be forced to differentiate directly into a specific lineage in vitro, so it does not involve what?

the creation of a human embryo