Epigenetics, Stem Cells & Development Flashcards
For multicellular organisms, tissue/organ formation and cell replacement depends on:
Specific patterns of cell division
Match the following terms to their definitions:
1) Symmetric division
2) Asymmetric cell division
3) Cell lineage
4) Lineage tracing
A) the developmental history of a differentiated cell as traced back to the cell from which it arises.
B) two daughter cells are identical to each other and to the parent cell
C) labels cells (ex: fluorescent label) and track the progress of cell division + differentiation
D) two daughter cells may differ in size, shape, protein composition, gene expression and have different fates: they can be different from the parent cell and from each other OR one daughter identical to parent, other daughter cell different.
Symmetric division: two daughter cells are identical to each other and to the parent cell
Asymmetric cell division: two daughter cells may differ in size, shape, protein composition, gene expression and have different fates: they can be different from the parent cell and from each other OR one daughter identical to parent, other daughter cell different.
Cell lineage: the developmental history of a differentiated cell as traced back to the cell from which it arises.
Lineage tracing: labels cells (ex: fluorescent label) and track the progress of cell division + differentiation
For stem cell asymmetric division, what do the daughter cells look like?
One daughter - identical to parent stem cell
One daughter cell - matures into a differentiated cell type
Asymmetric cell division can enable _______ stem cell or __________ cell production or ___________ of stem cell production.
Increased; Differentiated; Maintenance
While a zygote is ___________, stem cells can be pluripotent or _________.
___________ stem cells take on cellular functions.
Totipotent (can be differentiated into anything)
Multipotent (can give rise to only some lineages)
Differentiated
What are hematopoietic stem cells (HSC)?
Hematopoietic stem cells are MULTIPOTENT stem cells that generate blood cells throughout an individual’s life.
HSC from human bone marrow can divide to produce more HSCs. HSC daughter cells are capable of becoming a different progenitor and differentiated cell types.
What are the five master transcription factors? How do they achieve their functions?
aka YAMANAKA factors: Oct4, Sox2, Nanog, KIf4, and Myc. These control ES (embryonic stem) cell pluripotency.
With the right combination of these, a cell can become any other kind of cell. They:
1) Activate genes for self-renewal, pluripotency
2) They repress genes that induce specific differentiation pathways
The master TFs bind to own promoter as well as to promoters of others, causing a ____________ __________ loop.
Positive autoregulatory
These activate transcription of each of these genes.
The master TFs also bind to the transcription-control regions of many ________ genes.
They _______ genes encoding proteins for the proliferation and self-renewal of ES cells.
They _________ genes that are typically silenced in undifferentiated ES cells and that encode proteins essential for the formation of many differentiated cell types.
downstream
activate
repress
What happens if the Yamanaka factors are virally inserted into differentiated fibroblasts?
The cells will de-differentiate into induced pluripotent stem cells (iPSCs).
Like embryonic stem cells, iPSCs can give rise to progeny of all _____ germ layers (________, ________, and __________)
Three; mesoderm, ectoderm, endoderm
Ectoderm (outer layer)
Mesoderm (middle layer)
Endoderm (internal layer)
*stem cells of fertilized eggs form three distinct embryonic germ layers (so do iPSCs)
(T/F) The ectoderm becomes skin, CNS, and pigment cells, while mesoderm becomes notochord, bones, kidney, head and RBCs, and endoderm becomes stomach, thyroid, and lung cells.
True!
Briefly describe medical uses of iPS cells.
If a patient has a disease caused at a molecular/cellular level like a neurodegenerative disorder caused by neurons (Amyotrophic lateral sclerosis), extracting neurons/glial cells from living humans can’t be simply extracted to analyze or culture.
Therefore if you take their skin cells, you can over express YAMANAKA factors and create iPS cells. These have two uses:
1) If you know the disease-causing mutation, you can GENE TARGET to repair the DNA sequence and differentiate the iPS into neurons affected by the disease and transplant these into the patient’s brain.
2) You can differianted the iPS cells into the affected neuronal subtype carrying mutation and test/screen for drugs that their neurons respond to best.
What are morphogens? What does its gradient help establish?
Morphogens are signals that induce different cell fates depending on their concentration at their target cells.
Morphogen gradients help establish CELL DIFFERENTIATION, the BODY AXES, ORIENTATION + PATTERNING of tissues and organs.
(T/F) Wnt and Hh are morphogens.
True!
What happens when morphogens diffuse farther and farther away from secreting cells?
Their concentration decreases.
Morphogen concentration induces different fates in target cells; cells that detect a large amount of morphogens turn on certain genes and form certain structures, while cells that detect a smaller amount turn on different genes and so form different structures.
While the Wnt RNA is expressed in both the anterior and posterior wound sites, the Wnt inhibitor ________ is only expressed at the _______ wound site in adult planaria.
This forms a ______-__-______ gradient of Wnt protein.
Notum; Anterior
Posterior-to-anterior
*planaria is a worm
*gradients of Wnt are essential for normal regeneration of a head and a tail by planaria
(T/F) After 14 days in culture, the excised body piece from the middle of the body of the planaria regenerates a normal, smaller, worm with a head from the posterior and a tail from the anterior.
False!
After 14 days in culture, the excised body piece from the middle of the body of the planaria regenerates a normal, smaller, worm with a head from the ANTERIOR and a tail from the POSTERIOR.
β-catenin, stabilized by addition of ____ to cells, causes expression of genes that promote _____ formation in planarians.
Inhibition of Wnt/β-catenin signaling by _____ causes a _____ to be formed.
Therefore, if you inhibit/lose β-catenin, you will have ____-_____ planarian.
If you inhibit Notum, you will have a _____-_____ planarian.
Wnt; tail
Notum; head
Two-headed planarian
Two-tailed planarian
What is a sonic hedgehog (Shh)?
Sonic hedgehog (Shh) is a morphogenetic ligand of the Hh pathway. As a morphogen, its protein polarizes the developing limb.
Sonic hedgehog is expressed in the nervous system, gut and the limb bud and carniofacial structures of a 3-day chick embryo.
What happens when you implant the Shh-producing cells into the anterior of the developing limb?
You mirror duplication of posterior of the developing limb.
The anterior begins to develop like the posterior of the developing chick wing.
What happened to the sheep that ate Veratrum Californicum early in pregnancy?
The alkaloid (cyclopamine) made by the plant inhibits cholesterol synthesis, which is needed for Hedgehog production and reception.
Shh is expressed in the developing face. Inhibiting its production and reception led to a one eye sheep, a cyclops.
Match the following genes of dorsophila melanogaster to their definitions:
1) Maternal Axis-determining genes
2) Gap genes
3) Pair-rule genes
4) Segment polarity genes
5) Homeotic genes
A) Enable the expression of pair-rule genes. When you mutate these genes, the whole genes are gone; resembling a gap.
B) Divide the embryo into segment-sized units along the anterior-posterior axis.
C) Deposited by the female fly. These form gradients and regions of MORPHOGENETIC proteins. These proteins are TFs that activate the gap genes.
D) Master regulator genes that direct the development of particular body segments or structures.
E) Divides the embryo into regions about two segments wide into a series of stripes (odd/even).
1) Maternal axis-determining genes: Deposited by the female fly. These form gradients and regions of MORPHOGENETIC proteins. These proteins are TFs that activate the gap genes.
2) Gap genes: Enable the expression of pair-rule genes. When you mutate these genes, the whole genes are gone; resembling a gap.
3) Pair-rule genes: Divides the embryo into regions about two segments wide into a series of stripes (odd/even).
4) Segment polarity genes: Divide the embryo into segment-sized units along the anterior-posterior axis.
5) Homeotic genes: Master regulator genes that direct the development of particular body segments or structures.
The different genes (axis-determining, gap, pair-rule, segment polarity) define the _______ _______ of the ______ genes that define the identities of each of the segments.
Spatial domains; homeotic
What are bicoid and nanos?
What do they activate?
Bicoid and nanos are morphogens that are originally depostied as mRNAs by the mother fly.
These translate into morphogens and form a COORDINATE SYSTEM based on their RATIOS.
Each position along the axis is distinguished from any other position. When the nuclei divide, each nucleus is given its positional information by the ratio of the proteins.
These gradients activate the TRANSCRIPTION of genes specifying the segmental identities of the larva and the adult fly.
Theres a greater concentration of bicoid in the ______ position of the fly and a greater concentration of nanos in the ________ position.
Anterior; Posterior
What is “find it, move it, lose it”?
It is a saying that determine what certain genes do:
Find where genes are expressed
Move the genes to where they are not expressed; WHAT CAN THEY DO WHERE THEY DON’T BELONG?
Lose the gene by mutating the gene; WHAT IS IT NECESSARY TO DO?
Give an example of “find it, move it, lose it”.
For example: Bicoid mRNA is located in the anterior side (FIND IT).
When you add bicoid in the middle of embryo, a head forms in the middle and tails form in the ends (MOVE IT).
When bicoid is removed (LOSE IT); a tail forms in the anterior side.
Looking at the experiment, we can tell that bicoid promoters anterior formation and suppresses posterior formation.
What is the even-skipped gene?
Even-skipped is a PAIR-RULE GENE.
Specific promoter regions of the even-skipped gene control specific transcription bands (stripes 1-7) in the embryo.
The enhancer element for stripe 2 in the even skipped gene contains binding sequences for several _______ and ______ gene proteins.
maternal; gap
(T/F) In the even-skipped gene, every activator site is closely related to the repressor site, suggesting COMPETITIVE INTERACTIONS at these positions.
True!
Moreover, a protein that is a repressor for stripe 2 may be an activator for stripe 5; it depends which proteins bind next to them.
Wings of the wild-type fruit fly emerge from the _______ __________ segment.
A four winged fly is constructed by putting together _____ mutations in cis-regulators of the ____________ gene.
These mutations transform the ____ thoracic segment into another _____ thoracic segment.
Second thoracic
3; Ultrabithorax
third; second
(T/F) In the center of hox genes, there are genes of the antennapedia and bithorax complexes.
True!
