Lecture 15 - Stem Cells: Basic Concepts Flashcards by Cale Dobrosak

Develpoment from blastocyst involves a series of fate choices, what does the epiblast give rise to?

The 3 germ layers:

Endoderm
mesoderm
ectoderm

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Determination and differentiation results not from changes in genes, but…

changes in gene expression (exception being immune system and gametes)

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What makes this change in gene expression?

alterations in chromatin structure and transcription factor expression

Often quite permanent and heritable through many cell divisions

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Determination occurs prior to overt…

differentiation - heritable change in a cell’s developmental potential -operationally defined

cells don’t LOOK like the cells they will become, but have made the decision to do so

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What is differentiation?

results of the change in gene expression

cells acquires correct shape polarity, orientation with respect to neighbour, appropriate organelles and proteins which enable it to carry out metabolic signalling, transport or contractile signalling, transport or contractile functions required in a partilcular tissue3

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What is transdifferentiation?

cell normally committed to one lineage is switched to a different lineage pathway

Many known examples from disease states - intetinal metaplasis of the esophagus

May be induced experimentally by ectopic expression of master regulator transcription factors

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Describe Intestinal metaplasia, and how it is caused?

What can it lead to?

Damage to esophageal epithelium through acid reflux from the stomach leads to conversion of squamous epithelium into intestine

The condition is a precurosor to esophageal adenocarcinoma

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Define a multipotent cell

cell that can give rise to several types of mature cells - not that many, limited.

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Define a pluripotent cell

Cell that can give rise to ALL types of adult tissue cells plus extraembryonic tissue: cells which support embryonic development

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Define a totipotent cell

cell that can give rise to a new individual given appropriate maternal support - Restricted to the blastomeres; the early cells of the embryo

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What are the different types of adult tissue, with respect to renewal?

continuously renewing - bone marrow, skin, gut

Conditionally renewing - liver, kidney

Non renewing - cardiac muscle

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We lose __ billion cells per day

20 billion

The lining of the intestineis replaced every 4 days

every 4 weeks a completely new epidermis is generated

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some tissues turn over slowly, e.g?

hepatocytes live for 300 days, cardiomyocytes 0.5% annually

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One blood stem cell gives rise to…

red cells, white cells and platelets

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Stem cells may give rise to transit amplifying cell compartment, what is this?

group of commited cells with limited division capacity

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Stem cells are often lacking in ____ _____

specialised organelles, and show high nucleus/cytoplasm ration

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What makes stem cells live long?

express telomerase - helps with keeping DNA intact

Stems cells live in anatomically specific zones called

niches

Proper tissue organisation and response to demands of growth or repair require that there be restrictions on…

developmental potential of adult stem cells

limits are strictly imposed by powerful molecular constraints on gene expression and are heritable during many rounds of cell division (epigenetics)

What is needed to from a cell to prove it is a stem cell?

ability to repopulate a issue and give rise to differentiated progeny as well as more stem cells

identified in transplantation assays with marked cells

There are a range of cell surface markers, specifially expressed at certain stages in the lineage - what is the use of this?

Useful in diagnosis - expressed on corresponding malignancies that are ‘hung up’ at specific stages in the lineage

Recent findings show that tissues formerly thought to be static in adult life contain…

stem cell popoulations - examples include heart and CNS

_____ are born constatntly throghuout life in specific brain region

Neurons

Where deoes adult neurogenesis occur?

subventricular zone and hippocampus - new neurons from SVZ wind up in the olfactory epithelium

Hippocampal neurogenesis may have a role in...

learning and memory

The four types of differentiated cell in the adult gut are formed constantly from ..

stem cells in the crypts - deep inside the tissue very characteristic structure

Wnt signalling and notch signalling can....

modulate the stem cells in crypts

Extrinsic signaling from surrounding cells reguatles..

stem cell proliferation

In continuously renewing cells, The long term repopulating cells in a tissue are often ______ What do they give rise to?

Quiescent - ticking over very slowly They then give rise to active stem/progenitor cells which move out from that region (i.e hair cell can move to to epidermis or down to the shaft)

Conditionally renewing cells Liver can regenerate by ..

proliferation of hepatoctyes, or from bipotential stem cells found in the biliary tree hepatocytes, just re-enter the cell cycle

What happens in biliary atresia?

blockage of bile duct, accumulation of bile in the liver and cirrhosis Bipotential biliary cells proliferate in an attempt to repair the damage

What are the 3 sources of pluripotent stem cells?

directly from embryos (ICM) Can make from adult stem cells with reprogramming somatic cell nuclear transfer (SCNT)

What is the process of SCNT?

take an egg, remove genetic material, put an adult cell nucleus back in and the egg can then reprogramming the adult cell nucleus back to its develpomental state, such that it can recapitulate all the process of animal development stop at a point (don't want to make a cloned human), and take the cell

What are the properties of pluripotent stem cells

grow indefinitely in vitro maintain normal genetic makeup - not getting cancer-line changes cloned lines capable of differentiation into a wide range of somatic and extra embryonic tissue in vivo and in vitro-at high frequency and under and range of conditions capable of colonising all tissues including germ line after blastocyst injection to give chimeric offspring

What are the key ethical points about the blastocyst stage of development?

body plan not yet apparent many cells will not form new human, but will give rise to tissue such as placenta which support pregnancy Embryo does not necessarily represent a unique individual (twins can still form) No precursors of nervous system yet Not possible to predict whether embryo will be able to develop to term

Teratomas are a way of showing..

pluripotency A teratoma is a tumor with tissue or organ components resembling normal derivatives of more than one germ layer. can inject into a mouse with no immune system to test whether the cells cells that were isolated are indeed pluripotent

What are seven signalling system s that control animals develpoment:

WNT HEDGE HOG NOTCH TGF BETA TYR KIN JAK-STAT NUCLEAR REC

ES cell differntiation goes though germ layer _______

intermediates - knowing the signalling pathways to these intermediates can hep get what we want in a research context

many species of mammal have now been cloned Can cloning technology be use to surmount immunological barrier to stem cell transplantation?

yes, pluripotent cells can be grown from iPSC

SCNT is very difficult to get right to make dolly, there were ___ separate attempts

200

What are the key applications for pluripotent stem cells in biomedical research?

basic studies of early human development and it's disorders-birth defecs, childhood cancers Functional genomics in human cells Discovery of novel factors controlling tissue regeneration and repair In vitro models for dug discovery and toxicology

Schizophrenia, autism and epilepsy are disorder of brain develpoment - what can be used to study them?

ES and iPS cell can model human cortical development iPSC from patients with these diseaase can be used to recapitulate key events in pathogenesis