STEM Cell Biology Exam 1

STEM CELL PARADIGM

Stem cells self-renew and make distinct progeny that become differentiated cells

The ability to grow stem cells opens possibilities to:

• cultivate cells for therapy → use for regenerative medicine

• study the mechanisms of development and gene control

• perform drug testing and toxicology assessments

REGENERATIVE MEDICINE

clinical use of stem cells or methods to elicit stem cell properties

• delivery of stem cells from culture

• delivery of engineered tissues and organs

• stimulation of endogenous regenerative response with precise molecular agents

CELL IDENTITY DOGMAS - Somatic Cells

o comprise all parts of the body outside germ cells

o divides by MITOSIS = DNA copied followed by a single nuclear division event

o divide to produce two genetically identical offspring cells that possess the same number

and kind of chromosomes as the original cell

o offspring are phenotypically identical to the parent cell

CELL IDENTITY DOGMAS - Germ Cells

o dedicated lineage in the body that produces differentiated gametes for reproduction

o divides by MEIOSIS = DNA copied followed by sequence of two nuclear divisions

o divide to produce one or more gametes that are genetically different from the parent:

▪ ploidy = chromosome copy number is reduced by half = REDUCTIVE division

▪ randomized sorting of chromosome groups that originated from egg (maternal) and

sperm (paternal) sources that founded the individual

▪ individual chromosomes may contain mixtures of maternal and paternal DNA sequence

due to recombination events that occur in meiosis I

o offspring are phenotypically different than the parent cell

CELL IDENTITY DOGMAS - Stem Cells

o divides by MITOSIS to produce genetically identical offspring cells

o offspring may be phenotypically identical to the parent cell, OR phenotypically different

o division can be asymmetric = make 2 unique offspring

o division can be symmetric = make 2 identical offspring

o drive development by making:

▪ somatic cells including tissue specific adult stem cells

▪ germ stem cells which produce gametes

o defined by experimental evidence that they can self-renew and make distinct progeny:

▪ self-renew = mechanisms to maintain a stable cell identity following mitosis, but this is not

immutable or fixed

▪ make distinct progeny = mechanisms to diversify identity of offspring cells

Fundamental Key Terms - Stem Cells

precursor = unspecialized = immature = key job is producing cellular offspring

o generate the embryo → all tissues and organs during development

o maintain various tissues during adulthood and/or enable regeneration

Fundamental Key Terms - Differentiated Cells

have specialized physiological role(s) = mature = terminally differentiated

o animals are comprised of several hundred (e.g. range of 100-250, or more)

o differentiated state is stable = terminal refers to the end of the developmental path = serve

discrete physiological jobs and the only option left is to die

Fundamental Key Terms - All Cells

exhibit unique traits = features can include morphology or form (size, shape, color);

motile/migratory; stationary; mesenchymal; epithelial; organelle number and arrangement;

membrane potential (electrical character); metabolic activity (chemical composition);

molecular components like RNA and protein; responsiveness to environment/signals;

ability to secrete signals

Fundamental Key Terms - Potency

all the fates possible for a cell

o development is a process of potency restriction

o totipotent → pluripotent → multipotent → sometimes as specific as unipotent

Fundamental Key Terms - Differential gene expression

different cells express different gene sets → dictate cell identity & function

o housekeeping genes = encode shared features across cells = e.g. machinery for mRNA translation

o unique genes = encode specific products that dictate unique character of a given cell type

o gene expression is regulated at 5 major levels:

▪ transcription, RNA processing, RNA transport, translation, protein modification

▪ transcriptional regulation is extremely important

o regulatory (control) regions dictate gene expression → are bound by transcription factors = types

of proteins that regulate the synthesis of RNA from DNA during the process of transcription

▪ promoters = DNA sequences located near gene coding region

▪ enhancers = DNA sequences located distant from gene coding region

Gametogenesis

o production of specialized gametes by meiosis

▪ their unique features enable proper gamete joining & species recognition

Fertilization

o steps involved with getting the gametes fuse → zygote !

o zygote = an ultimate stem cell that fuels the making of all body cells and in some cases, some

‘extra’ = extraembryonic tissues that support the growth of the embryo

o cell offspring of the zygote are progressively limited to different fates as development occurs

o PROGRAMMING = concept of establishing various cell identities through the gradual process of

differentiation which will occur as the zygote undergoes subsequent cell division

Cleavage

o early rounds of cell division that rapidly partition the zygote → blastula = ball of cells

o turn 1 cell in several hundred that are used to start making layers of the body

Gastrulation

o reorganize blastula → gastrula

o form the 3 germ layers = ectoderm, endoderm, mesoderm, AND segregate germ cell lineage

o body plan is established = includes emergence of anterior-posterior and dorsal-ventral axes

o ectoderm = outer layer

▪ examples: make skin, nervous system, neural crest

o mesoderm = middle layer

▪ examples: make muscle, bone, blood, kidney

o endoderm = innermost layer

▪ examples: make gastrointestinal tract and other organs in thoracic and abdominal cavities

Organogenesis

germ layers → subdivided and diversified further to make organs

Hatching → larval stages → adult

o hatching is an emergence from embryonic membrane(s), egg, or uterus = birthing event

o as an organism ages, it will undergo continued changes, many of which are fueled by long lived

adult stem cells