Cell Basis Of Embryo Flashcards
(175 cards)
1
Q
Stem cells have the property of __-__ through symmetric or asymmetric cell divisions
A
Self renewal
2
Q
What can stem cells give rise to
A
All differentiated cell types in the body (totipotent or pluripotent)
3
Q
Embryonic stem cells(ESC) what are they derived from
A
Inner cell mass of the blastula
4
Q
What are ESC and what can they give rise to
A
Pluripotent and give rise to all differentiated cell types from the ectoderm, endoderm, and mesoderm, the primary germ layers, but do not contribute to extraembryonic tissues
5
Q
What do ESC express
A
Transcription factors
SOX2 and OCT4, Nanog, FoxD3they repress differentiation
-GCNF is required for early stages of pluripotent cell differentiation
Crypto and GDF3 are growth factors found in pluripotent cells
Regulated by oct3/4 sox2, myc and klf4
6
Q
Adult stem cells: where are they found
A
In differentiated tissues and organs thatundergo rapid regeneration, such. As bone marrow, hair follicles, and intestinal mucosal epithelium
7
Q
However, there are nests of adult stem cells in may other tissues, including those that have been previously considered nonregnerative, such as the central nervous system and retina
A
These stem cell populations are small and located in the subventricular zone and ciliary margins, respectively
8
Q
Where are hematopoietic stem cells
A
Derived from bone marrow, peripheral blood, and umbilical cords
9
Q
What are hematopoietic stem cells used for
A
Treat primary immunodeficiency and various inherited metabolic disorders and as a rescue strategy following marrow destroying cancer treatments
10
Q
Cancer stem cells
A
Have becomes evident through study of leukemia’s and solid tumors. They are resistant to cancer treatments such as radiation or chemotherapy
11
Q
What cell surface markers do CSC have
A
CD133 in solid tumors
12
Q
What is the focus on CSC research
A
Eradicating them, in addition to standard therapies in order to increase cure rates
13
Q
It is possible to harness the power of stem cells to repair degenerative disorders like Parkinson and ischemia, but why is it limited
A
Sources of stem cells
14
Q
Induced pluripotent stem cells (iPS)
A
De differentiating somatic cells such as epithelial cells and fibroblasts from adults
15
Q
What transcription factors can reprogram differentiated cells into pluripotent cells
A
OCT3/4, SOX2, KLF4, Nanog
16
Q
IPS stem cells have the capacity for self renewal, cell death, or to become progenitors. What can progenitors do
A
Limited capacity for self renewal, but also can differentiate into various cell types or undergo cell death
17
Q
Histone methylation is done by __ __
A
Histone methyltransferases (writers)
18
Q
What is methylated
A
Histone Lysine arginine
19
Q
Is methylation activating or repressing
A
Can be both
20
Q
Example of Histone activation
A
Trimethylation of lysine 4 on Histone 3 (H3K4me3)
Active promoters
21
Q
Example of methylation repressing
A
Trimethylation of lysine 9 on Histone 3 (H#K9me3) repressed promoters
22
Q
Acetylation of Histone
A
DNA is less tightly bound to acetylated histones, thus allowing more open access of transcription factors and other proteins to the promoters of their targets
Activation of gene transcription
23
Q
Phosphorylation of histones
A
Also leads to an opening of the chromatin structure and activation of gene transcription
24
Q
Acetylation and phosphorylation are both read by ___ proteins and ___ ___ __ proteins
A
Bromodomain
Pleckstrin homology
25
Where is DNA methylated
CpG islands where cytosine and guanine are directly paired
26
Where are CpG islands usually located
Proximal promoter regions of genes
27
DNA methylation at CpG islands leads to what
Reduced gene expression
28
DNA hypomethylation at CpG islands
Gene overexpresion
29
Methyl-CpG-binding protein 2(MECP2)
Mutated in the neurodevelopmental disorder Rett syndrome, function as readers by binding to methylated DNA and subsequently assembling protein complexes that repress gene expression
30
What are some disorders of chromatin remodeling
Rett, Rubinstein-Taybi, alpha-thalassemia/X linked mental retardation syndromes
31
What are basic helix-loop-helix transcription factors
BHLH genes are a classs of transcription factors that regulate cells ate determination and differentiation in many different tissue during development
32
BHLH proteins contain a __(_charged) DNA binding region that is followed by two a helices that are separated by a loop
Basic +
33
In BHLH the a helices have. ___ and a __ side (amphipathic)
Hydrophilic and hydrophobic
34
The hydrophobic side of the a helix
Motif for protein-protein interactions between different members of the BHLH family
MOST CONSERVED
35
BHLH proteins often bind to other BHLH proteins (__) to regulat transcription
Heterodimer I’ve
36
BHLH heterodimers are composed of tissue specific BHLH proteins bound to ubiquitously expressed BHLH proteins
Ok
37
How can the prodifferentiation effects of BHLH genes be repressed
Inhibitor of differentiation proteins (Id) proteins are HLH proteins that lack the basic DNA binding motif. When Id proteins heterodimerize with specific BHLH proteins, they prevent binding of these BHLH proteins to their target gene promoter sequences (called E boxes)
38
Growth factors which tend to inhibit differentiation, ___ the level of Id proteins that sequester bHLH proteins which inhibits their ability to bind DNA
Increase
39
In addition , growth factors can stimulate the phosphorylation of DNA binding domain of bHLH proteins which does what
Inhibits their ability to bind DNA
40
BHLH genes are crucial for development of tissues such as muscle(__/__) and neurons (__/__) in humans
MyoD/Myogenin
| NeuroD/Neurogenin
41
MyoD
Can transdifferentiate several different cell lines into muscle cells
MASTER REGULATOR of muscle differentiation
42
Knockout MyoD and other bHLH, Myf5
Crucial for the differentiation of precursor cells into primitive muscle cells (myoblasts)
43
Mash1/Ascl1 and Neurogenin1
Proneural genes that regulate the formation of neuroblastoma from the neuroepithelium
44
Mash1/Ascl1 knockout
Defects in forebrain development
45
Neurogenin1 knock out
Defects in cranial sensory ganglia and ventral spinal cord neurons
46
Muscle and neuronal differentiation are controlled by a cascade of ___ genes that function at early and at late stages of cellular diferentiation
BHLH
47
The differentiation of muscle and neuronal cells are inhibited by what pathway
Notch
48
Pax genes all contain conserved ___ DNA binding motifs called the Pax domain, and most Pax family members also contain a ___
Bipartite
| Homeodomain
49
PAX proteins do what
Repress or activate transcription of target genes
50
Pax6
Eye development drosophila
| Aniridia and Peters anomaly in humans
51
In human eye diseases, the level of PAX6 expression seems to be crucial because why
Patients with only one functional copy(haploinsuffiency) have ocular defects and patients without PAX6 function are anophthalmic
52
PAX3 and PAX7encode both what
Homeodomain and PAX DNA binding domains
53
Rhabdomyosarcoma
Results from translocation that results in the formation of a chimeric protein wherein PAX3 and PAX7 is fused to the strong activating domains of the Forkhead family transcription factor FOXO1
54
Waardenburg syndrome type 1 (AD)
Mutation in PAX3 gene
| Hearing deficits, ocular defects, and pigmentation abnormalities best typified by. A white forelock
55
HOX/Homeobox proteins
Mutations -dramatic phenotypes such as antennapedia gene, in which legs instead of antennas sprout
56
In humans and drosophila, the order of HOX genes along the chromosome is
Conserved
57
Defect in HOXA1
Impair human neural development
58
HOXA13 and HOXD13 mutations
Limb malformations
59
All HOX genes contain a __ base pair sequence, the homeobox which encodes what
180
| A 60 aa homeodomain composed of 3 a helices
60
The third a helix of the homeodomain does what
Binds to DNA sites that contain one or more binding motifs int he promoters of their target genes
61
Mutations in DNA binding region of homeobox gene NKX2.5
Cardiac atrial septal defects
62
Mutations in ARX
Central nervous system malformation syndrome known as lisencephaly
63
Notch signalling pathway
Integral for cell fate determination, including maintenance of stem cell niches, proliferation, apoptosis, and differentiation
Essential for all aspects of organ development through regulation o lateral and inductive cell cell signaling
64
What are notch proteins
Single transmembrane receptors that interact with membrane bound notch ligands (delta like ligands and serrate like ligands) on adjacent cells
65
In notch, ligand receptor binding triggers proteolytic events leading to the release of the notch intracellular domain (NICD). What happens when NICD translocates to the nucleus
Series of intranuclear events culminates in raw induction of expression of a transcription factor that maintains the progenitor state of the cell
66
In notch, lateral inhibition ensures the correct number of two distinct cell types from a population of cells with equivalent developmental potential
Ok
67
Notch: in the initial cell cell interaction, notch receptor signaling maintains one cell as an uncommitted progenitor
Ok
68
The adjacent cell maintains reduced notch signaling and undergoes differentiation
Inductive signaling with other surrounding cells expressing morphogens may overcome a cells commitment to a default fate and lead to an alternative cell fate
69
Mutations in Jagged1 (notch)
Alagille syndrome (arteriohepatic sysplasia) withe liver, kidney, and that notch3 gene mutations are found in CADSIL, an adult vascular degenerative disease with a tendency to early age onset of stroke like events,
70
During embryogenesis, signalling through )) is crucial for normal development and affects many different processes such as what
Growth of new blood vessels, cellular migration , And neuronal atonal guidance
71
Growth factors generally promote cellular proliferation, migration and survival
During embryogenesis, signaling through FTKs is crucial for normal development and affects many different processes such as the growth of new blood vessels, cellular migration, and neuronal atonal guidance
72
What binds to RTK
Insulin, epidermal growth factor, nerve growth factor, neurotrophins, platelet derived growth factor
73
What are the 3 domains of RTK
Extracellular ligand binding domain
| Intracellular kinase domaintransmembrane domain
74
RTK are _ in the unbound state and __ whene bound to ligand
Monomer
| Domers
75
What does dimerization upon binding to a ligand do for RTK
Brings two intracellular kinase domains in close proximity such that one kinase domain can phosphorylation and activate the other (transphosphorylation) which is required to activate the receptor..
76
What happens after RTK transphosphorylation
Series of intracellular signaling cascades.
77
What happens if there is an inactivating mutation of one resceptor subunit kinase domain of RTK
Abolishment of signaling
78
Mutation in the kinase domain of VEGF receptor 3 (VEGFR3)
AD
| Inherited lymphatic disorder called Milroy disease
79
What do growth factors do
Promoter cellular proliferation, migration and survival
80
During development, RTK is crucial for normal development. What does it effect
Different processes, such as growth of new blood vessels, cellular migration and neuronal atonal guidance
81
What do hemangioblasts give rise to
Hematopoietic cell and endothelial cell
82
The early endothelial cells proliferate and eventually coalesce to form the first primitive __ ___. What is this called
Blood vessels
| Vasculogenesis
83
What happens after the first blood vessels are formed
Intensive remodeling and maturation into the mature blood vessels in a process called angiogenesis
84
Vasculogenesis
Formation of vessels
85
Angiogenesis
Maturationa nd remodeling of blood vessels
86
Angiogenesis involves the recruitment of vascular __ __ cells to the vessels to stabilize them
Smooth muscle
87
Vasculogenesis and angiogenesis are both dependent on the function of two distinct __ classes, members of the ___ and ___ receptor families
RTK
VEGF
Tie
88
__ is essential for endothelial and blood cell development
VEGF-A
89
VEGFA knock out
Fail to develop blood or endothelial cells and die at an early embryonic stage
90
___ is crucial for development of lymphatic endothelial cells
VEGFC
91
VEDGA signals through three receptors, where are they and what are they’re
VEGFR-1, 2 and 3
| On endothelial cells
92
The process of angiogenesis refinement depends not he function of angiopoitein/tie2 signaling pathway
Tie2 is a RTK that is specifically expressed by endothelial cells and angiopoietin 1 and angiopoietin 2 are its ligands that are expressed by surrounding vascular smooth muscle cells
93
What kind of signaling it angiopoietin/tie2
Paracrine
94
Both VEGF/VEGFR3 and angiopoietin/tie2 are co-opted by __ to stimulate growth of new blood vessels
Tumors , which in turn stimulate their growth and metastisis
95
Wnt
Morphogen, 19 wnt family members control several processes during development
Establish cell polarity, proliferation, apoptosis, cell fate specification, and migration
96
B-catenin wnt pathway
Wnt binds to 1 of 10 frizzled seven transmembrane domain cell surface receptors, and with low density, lipoprotein receptor-related proteins 5 and 6 (LRP5/LRP6) coreceptors,t thereby activating downstream intracellular signaling events
97
Absence of Wnt binding
Cytoplasmic B catenin is phosphorylation by glycogen synthase kinase 3 (GSK-3) and targeted for degradation
98
In the presence of wnts , GSK3 is inactivated and B catenin is not phorphorylated . What happen
B catenin accumulated in the cytoplasm and translocated to the nucleus where it activates target gene transcription in a complex with T cell factor transcription in a complex with T cell factor transcription factors
(TCF)
99
Bcatenin/TCF target genes
VEGF and matrix metalloprotease
100
Dysregulated Wnt
Developmental disorders
William-beuren syndrome (heart, neurodevelopmental, and facial defects)
Cancer
101
LRP5 mutations
In osteoporosis -pseudoglioma syndrome -congenital blindness and juvenile osteoporosis
102
Shh and Wnt mutations
Medulloblastoma , a common malignant brain tumor
103
Sonic hedge hog shh
Secreted morphogens critical for early patterning, cell migration and differentiation of many cell types and organ systems
104
Receptor for shh
Pathed (PTCH), a transmembrane domain protein
105
Absence of shh
Patched inhibits transmembrane domain, G protein linked protein(smoothened smo)
106
Inhibition of smo
Inhibits downstream signaling to the nucleus by shh
107
Presence of shh
Ptc inhibition is blocked and downstream events follow, including transcriptional activation of target genes such as ptc1, engrailed and others
108
Post translational modification of shh affects what
It’s association with the cell membrane, formation of shh multi era, and movement of shh which alters its distribution and concentration gradients
109
Shh is secreted in high levels in the ___
Notochord
110
The concentration of shh is highest where and lowest where
In the floor plate of the neural tube and loft plate
111
What is high in the roof plate
Where members of tgfb
112
The cell fates of the ventral interneuron classes and odor neurons are determined by the relative shh concentrations in the tissue and other factors
Ok
113
Mutations of shh and ptch
Holoprosencephlay -fusion of the two cerebral hemispheres, dorsalization of forebrain structures and anopthalmia or cyclopia
114
___ sidrupts shh signaling
Cycloplamine
115
Gorlin syndrome
Germline mutation in ptch
| Constellation of congenital malformations mostly affecting epidermis, craniofacial structures and nervous system
116
Mutations in GLI3, encoding a zinc finger that mediates shh signaling
AD polydactylyl syndromes
117
What happens when GLI translocated to nucleus
Activate target gene with CBP
118
What us sufu
Suppressor of fused
119
Tgfb superfamily includes what
Tgfb, bmp, and activin
120
What do tgfb superfamily do
Establish dorsoventral patterning, cell fate decisions, and formation of specific organs and systems, including kidneys , nervous system, skeleton, and blood
121
In humans what are the three forms of TGFB
TGFB1, 2, 3
122
What happens when tgfb superfamily bind to ligands to transmembrane kinase receptors
Phosphorylation of intracellular receptor associated Smad proteins (R-Smads)
123
Smad proteins
Large family of intercellular proteins that are divided into the press classes
124
What are the three classes of Smad
```
Receptor activated (R-Smads)
Common partner(Co-Smads)
Inhibitory (I-smads)
```
125
R-Smad/Smad4
Regulate target gene transcription by interacting with other proteins or as transcription factors by direct binding to dna
126
What is the bioactive form of vitamin a
Retinoids acid
127
How it retinoids acid formed from vitamin a
Enzymatic oxidation by retinol aldehyde dehydrogenase and subsequently retinal aldehyde dehydrogenase
128
Free levels of retinoids acid can be modulated by cellular retinoids acid binding proteins which ___ it
Sequester
129
Retinoids acid can be actively degraded into inactive metabolites by enzymes such as __
CYP26
130
Normally retinoids acid acts to __ the body plan
Posteriorize
131
Excessive retinoids acid or inhibition of its degradation
Truncated body acid where structures have.a more posterior nature
132
Insufficient retinoids acid or defects in enzymes (retinal eldehyde dehydrogenase)
More anteriorized structures
133
Retinoids acid binds to receptors __ (transcription factors)the cell and their activation will regulate expression of downstream genes
Inside
134
__ genes are a crucial target of retinoids acid receptors in development
HOX
135
When are retinoids powerful teratogens
1st trimester
136
Extrinsic signaling by ___ guides the differentiation and migration of cells during development , determining the morphology and function of developing tissues and organs
Morphogens
137
Many morphogens rare found in __ __ int he embryo
Concentration gradients
138
Cells can be attracted or repelled by morphogens depending on what
Receptor on the cell
139
Different morphogens can be expressed in opposing gradients in the __ and ___ and ___ axes
Dorsoventral
Anteroposterior
Mediolateral
140
Gap junctions permit what to go though
Ions and small molecules less than 1 I’d
141
What is a connexon
6 connexin
142
In early development gap junctions are usually ___. Why
Open permitting exchange of small molecules in a relatively large region
143
As development proceeded GJIC is more ___ why
Restricted
| Establish boundaries such as in the rhombohedra’s of the developing hindbrain
144
Mutation in connexin Cx43
Atherosclerosis
145
Cadherine
Critical for embryonic morphogenetic as they regulat separation of cell layers (endothelial and epidermal), cell migration, cell sorting, establishment of well defined boundaries, synaptic connections and in growth cones of neurons
146
Cadherine mediate interaction between the cel and what
It’s extracellular milieu
| -neighboring cells and extracellular matrix
147
/Where is e cadherin? N cadherin?
Epithelial
| Neural cells
148
Describe the typical cadherin molecule
Large extracellular domain, a transmembrane domain and an intracellular tail
149
Describe the cadherin extracellular domain
Has five extracellular repeats and has four ca binding sites
150
Cadherine form __ that interact with cadherin __ in adjacent cells
Dimer diners
151
Where are cadherine found
Adhering junctions -tigh barrier
152
Via its intracellluar domain, cadherin binds to ___, __ and ___
P230-catenin, b catenin, and a catenin
153
What do p120, bcatenin and a catenin do
Connect cadherin to the cytoskeleton
154
When is e cadherin expression lost
As epithelial cells transition to mesenchymal (EMT)
155
What is EMT required for
Formation of NCC during development and the Sam process occurs in tumor development
156
What is a morphogen
Diffusable molecules that specify which cell type will be generated at a specific anatomical location
Also direct the migration of cells and their processes to their final destination
157
Name some morphogens
Retinoids acid, transforming growth factor b, bmp, shh, wnt
158
Characteristics of stem cells
Not terminally differentiated
Can divide without limit
Slow division
159
What happens when stem cells divide
1 cell with stem cell characteristics and other can differentiate
160
Adult stem cells
Tissue specific
161
Zygote
Totipotent
162
Embryonic stem cell
Pluripotent (blastocyst inner cell mass)
163
Multipotent
Adult stem cell
164
Founder stem cells
If the adult organ needs to be renewed, founder stem cells can divide as stem cells giving rise to one daughter cell that remains a stem cell and a set of cells that have a set number of transit amplifying divisions
Each tissue has fixed number of founder cell Polaroid. Programmed to have fixed number of divisions
Controlled by short range signals that operate for a few hundred cell diameter
Define size of large final structure
165
Transit amplifying cells
Divide frequently
Transit from a cell with stem cell to a differentiated
Leave basal layer and incorporate into other
Programmed to have limited number of divisions
-Growth control
166
How do we maintain stem cells
Divisional asymmetry-one is stem one can differentiate
Env asymmetry
-env may influence one cell after identical division
167
Immortal strand
Some tissues stem cells retain original dna
Preserved ins them cells from generation to generation
Second cell gets new strand
168
ESC risk if injected into adult
May become teratomas
169
Teratoma
No axis formation or segmentation
Es incapable of generating the body plan
No organization in es
170
How grow ES
Serum medium
Or serum free with serum replacement and FGF
171
Two methods for getting patient specific cells
Induced pluripotent patient (iPSC)or non patient derived (iPSC ESC)
172
Mesenchymal stem cell
Wharton jelly
Bone marrow
Adipose and tooth pulp
173
Neural stem cell
Can repopulate CNS
174
Induced pluripotent
After fertilization zygote undergoes equal divisions, totipotent. 4 days after become blastocysts. Inner cell mass is pluripotent
175
Somatic cell nuclear transfer
Remove nucleus of egg cell, put somatic cell of any type in the egg cell. Stimulate cell division and get inner cell mass a pluripotent embryonic stem cell
-can make pancreatic stem cells for transplant in diabetic
