Lecture A5, A6 Flashcards
Changes in cell fate are caused by _____
-heritable changes in gene expression
changes in gene expression are done by ______(4)
-Gene regulatory proteins (Coactivator,Corepressor)
-General transcription factors
-DNA methylation
-Histone methylation
aging is defined by _____
loss of stem cell population
stem cell: each daughters cell produced can _____
either remain a stem cell (self-renewal pathway) or become terminally differentiated
exceptions of stem cells
-both differentiate
-both remain stem cell
______ regulate how a stem cell divides into two daughters that have different fates
Intrinsic and extrinsic factors
extrinsic factors that determine fate of stem cell
-signalling proteins (morphogens)
-cell-cell contact
environmental asymmetry (def.)
-the location-dependent extrinsic factor that determine stem cell fate (aka differences in environment determine stem cell fate)
divisional asymmetry (def.)
-the intrinsic factor that determine stem cell fate (aka unequal cell division of cell contents like TFs determine stem cell fate)
morphogens can work directly in _______ or via _____
-receiving cells (steroid hormone)
-ligand/cell surface receptor pairing
morphogens are ____ that work through ______
-extrinsic factors
-autocrine signalling and concentration dependent response
concentration dependent response (def.)
concentration of substance (ex. morphogens) determines tissue patterning and cell differentiation
niche (def.)
all the environmental/extrinsic factors present for cell (determines cell fate)
when stem cell divide, the orientation of _____ plays a role in developing asymmetry
spindle apparatus
Transit amplifying cells are derived from ______
stem cell daughter that is committed to differentiation
Transit amplifying cells are not ___ but are _____ and divide multiple times before ____
-terminally differentiated
-committed
-becoming terminally differentiated
Stem cells remain in a ‘primitive’ state which means that _____
relatively few ‘terminal differentiation’ genes are
active
Commitment (def.)
one daughter starts expressing genes characteristic of a specific cell lineage
Lineage (def.)
-progressive cell division/differentiation events
leading to a specific type of terminally differentiated cell
Transit amplifying cells aka ______
committed progenitor cell
the production of a specific cell type might be regulated by these parameters: ____ (7)
- Frequency of stem cell division
- Prob. of stem cell death
- Prob that stem cell daughter will become committed progenitor cell
- Division cycle time of committed progenitor cell
- Probability of progenitor cell death
- number of committed progenitor cell division before terminal diff.
- Lifetime of diff. cells
stem cell (def.)
Undifferentiated cells that can, via selective cell division, proliferate (symmetric division) or
self-renew and differentiate (asymmetric division) to produce mature progeny cells
Totipotent (def.)
-can form all lineages of organism; can form an entire organism (ex. zygote and 1st cleavage blastomeres)
pluripotent (def.)
-can form all cells of the body but can’t form an entire organism (ex. embryonic SC)
multipotent (def.)
-adult stem cells that can form multiple cell types of one lineage (ex. hematopoietic SC)
unipotent (def.)
-cells form one cell type (ex. spermatogonial stem cells can only form sperm)
reprogramming (def.)
-increasing potency (aka dedifferentiation) that can be induced by nuclear transfer, cell fusion or genetic manipulation)
transdifferentiation, plasticity (def.)
the idea that somatic stem cells have broad potency and can create cells of other lineages (highly controversial in mammals)
3 types of SC
-embryonic stem cells (ESC)
-adult stem cells
-induced pluripotent stem cells (iPSCs)
despite the many sources of adult stem cells, they ____
all look similar (not morphologically different)
iPSCs are made from ______
fibroblasts using reprogramming factors
ESC are derived from ____
embryo inner cell mass of the human blastocyst
ESC can form ____ but cannot form ______
-can form all the cell types of a human fetus
-cannot form the extra-embryonic tissues
morula has this type of cells? blastocyst?
-totipotent
-pluripotent
stem cell pop’n in your body is typically ___
unipotent
During germ layer formation, signalling molecules act in 3D to _____ which ______
-induce the creation of the primitive streak
-gives rise to neural crest
Neural crest cells (NCC) are _____
-multipotent cells that migrate throughout the embryo and later differentiate into multiple cell types
NCC differentiate into: ______ (3)
-the peripheral system
-cranio-facial cartilage and bones
-pigment and endocrine cells
gastrulation leads to _____ SC becoming _____
-pluripotent
-multipotent
ESC injected into blastocyst become ____
incorporated into inner cell mass of host and forms a healthy chimeric cells
ESC experiences _____ as stem cells commit to a lineage
progressive changes in epigenetic marks
niche (def.)
a specialized environment within the adult body that maintains conditions such that cells can remain in an undifferentiated state (ex. bone marrow)
loss of niche = _____
loss of SC
the niche of adult stem cells are formed by ____ (3)
-paracrine + autocrine signalling
-surrounding matrix (ex. sugars, proteins etc.)
-other cells (ex. osteoblasts in bone marrow)
4 genes were necessary for the reprogramming for fibroblasts to form iPSC: ______
OCT3/4, SOX2, KLF4, and c-MYC
general lineage steps
1) stem cells
2) progenitor cells
3) precursor cells (blasts)
4) mature cells
lineage cells that have potentiality
1) stem cells
2) progenitor cells -least
lineage cells that have lot of mitotic activity
1) stem cells
2) progenitor cells
3) precursor cells (blasts)- highest
lineage cells that have self-renewing capacity
1) stem cells
2) progenitor cells- least
lineage cells that have typical morphological characteristics
1) precursor cells (blasts)
2) mature cells - most
lineage cells that have differentiated functional activity
1) mature cells
lineage cells that are unders greatest influence of growth factors
1) progenitor cells
2) precursor cells (blasts)
Hematopoietic stem cells (HSCs) (def.)
the stem cells that give rise to other blood cells
HSC are derived from this lineage?
mesoderm
HSC are produced first by _____ then by _____
-yolk sac (extraembryonic)
-embryo itself
Primitive HSCs are produced in _____
blood islands in the yolk sac (extraembryonic mesoderm)
Definitive HSCs are produced ______ and form _____
-in aortic region in the embryo
-long term HSC that migrates to bone marrow
The location of your definitive HSC _____
changes during your lifetime
at prenatal 1-2 months, HSC is where?
yolk sac
at prenatal 2-6/7 months, HSC is where?
liver & spleen
at 7-birth months, HSC is where?
bone marrow
postnatally, HSC is where?
-tibia, femur (till age 20-30)
-vertebra, sternum, rib
HSC in adult body _____ as you age
-decrease (biggest drop at 40)
HSC lineage example
1) long term HSC
2) short term HSC
3) multilineage progenitors
4) unilineage progenitors
5) terminally differentiated cells
Niche of HSC in bone marrow created by _______
-Osteoblast (secretes mineralized bone material)
-HSC
-Stromal Cells
-Extracellular matrix
-transit amplifying (TA) cells from other adult stem cell populations
stromal cells (def.)
-adult stem cells that can differentiate into osteoblasts, and other types of cells (mesenchymal)
Wnt & HSC
Wnt promotes HSC proliferation & differentiation
NOTCH & HSC
NOTCH promotes HSC proliferation & inhibits differentiation
HSCs are released from the bone marrow to replenish blood cells under the control of ______ and ______ which is why eating spicy food increasing HSC in blood
-involuntary nerves
-Pain-sensing nerves
general bone marrow niche
-HSCs
-MSCs (Mesenchymal stem cells)
-Osteoclasts break down bone (remodelling)
-Fibronectin (part of ECM)
-Endothelial cells (form the blood vessels)
MSCs (Mesenchymal stem cells) (def.)
-fibroblast-like cells that can differentiate into cells of several tissues
MSC differentiate into ______ (8)
-cartilage
-bone
-fat (adipose)
-muscle
-tendon
-hematopoietic supporting marrow stroma
-hepatocytes (less common)
-neural tissue (less common)
Intestinal stem cells (ISC) differentiate into ____ (4)
-paneth cell (secrete antimicrobial factors)
-enteroendocrine cell (secrete hormones)
-goblet cell (secrete mucous)
-enterocyte (absorb stuff)
Hair follicle stem cells (HFSC) differentiate into _________ (2)
-infundibulum cell (forms hair follicle)
-sebocyte (sebum cell)
Bmps/TGFB & ISC
Bmps/TGFB inhibits ISC proliferation
Wnt & ISC
Wnt promotes ISC proliferation
The skin increases in differentiation as it ____
goes up
secreted factors of skin epithelia
Wnt and EGF
Wnt & HFSC
Wnt promotes HFSC proliferation and prevent differentiation
Some adult stem cells are a dedicated cell population, and some can be _____
-induced ‘as needed’ by local changes in signaling and transcription
Satellite cells (def.) Following muscle damage, they begin both to _____
- a dedicated (professional) population of muscle stem cells
-self-renew and to terminally differentiate into
mature muscle cells called myofibres
The liver contains no known ______. Following damage, these unipotent progenitors can acquire _____ from which they can ______
-professional stem cells
-a bipotential progenitor state (facultative stem
cell)
-self-renew and give rise to both hepatocytes and duct cells
professional vs facultative SC
professional: always present/dedicated
facultative: unipotent ell turns back into progenitor to renew other cell types
