Stem Cells Flashcards by Joel Glotfelty

What properties define stem cells?

) They are unspecialized

2. ) The can be induced to differentiate into specific cells

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Are unspecialized and can self renew

Stem Cells

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Can be induced to differentiate into cells with special functions

Stem cells

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Predominates under steady-state conditions and serves to maintain a balance between differentiated and undifferentiated cells

Asymmetric division

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Predominate when stem cells must expand in number

-Ex: during development or injury

Symmetric divisions

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Asymmetrical segregation of factors that promote “stemness” to one daughter cell and not the other

Asymmetric division

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What essentially happens during asymmetric division?

2 cells are formed, one cell differentiates and and the other remains undifferentiated

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What are the two ways to regulate stem cell self-renewal

) Cell intrinsic regulation

2. ) Cell extrinsic regulation

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What are three transcription factors of cell-intrinsic regulation of stem cell self-renewal?

Sox2, Oct4, and Nanog

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Negatively regulate expression of differentiation-promoting genes

Sox2, Oct4, and Nanog

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Suppresses transcription of differentiation-inducing genes such as GATA4 and GATA6

-intrinsic regulator

Ronin (DNA binding protein)

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In the cell extrinsic pathway, LIF and BMP work through STAT3 and SMAD-Id to block the

MAPK pathway

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Blocking differentiation in stem cells leads to

Self renewal

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Describes the microenvironment in which the stem cells reside in their undifferentiated state

Stem cell Niche

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Tissue injury results in a respecification of the

Niche environment

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Respecification of the niche environment can result in increased

Proliferation and differentiation

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Stem cell division with maintenance of the undifferentiated state

Stem cell self-renewal

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An example of a stem cell niche is the

Intestinal crypt

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Stem cells in the intestinal crypt can give rise to

TA cells and Paneth cells

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Remain close in proximity to stem cells

-1:1 ratio with intestinal stem cells and stem cells won’t divide without them

Paneth cells

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What are the three types of stem cells

) Adult stem cells
) Embryonic stem cells
) Cancer stem cells

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An undifferentiated cell found in a differentiated tissue that can self renew and differentiate into all of the specialized cell types of the tissue from which it originated

Adult stem cell

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A type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing forced expression of specific genes

Induced pluripotent stem cells (iPS cells)

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Undifferentiated cells derived from a 5-day preimplantation embryo

-can differentiate into a wide variety of specialized cell types

Embryonic stem cells

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Cells that drive tumorigenesis and also give rise to differentiated progeny

Cancer stem cells (CSC)

A cell that through the process of differentiation has acquired a specialized structure and function

Differentiated cell

A cancer in which the cells are mature and look like cells in the tissue from which it arose

Differentiated cancer cell

A cell that has not yet acquired a special structure or function

Undifferentiated cell

A cancer in which the cells are very immature and "primitive" and do not look like cells from which it arose

Undifferentiated Cancer cell

A process by which a partially or terminally differentiated cell reverts to an earlier developmental stage

Dedifferentiation

The potential to differentiate is termed

Potency

Can give rise to embryonic and extraembryonic tissues -Exist up until 8 cell embryo

Totipotent stem cells

Descendants of totipotent stem cells that can differentiate into cells from any of the three germ layers

Pluripotent stem cells

An example of pluripotent stem cells are

ICM cells

Stem sells that can differentiate into a number of cells, but only those of a closely related family of cells -ex: hematopoetic stem cell

Miltipotent stem cells

Stem cells that can differentiate into only a few cells, such as lymphoid or myeloid stem cells

Oligopotent stem cells

When stem cells can produce only one cell type, their own, they are termed -ex: muscle stem cells

Unipotent stem

Unipotent stem cells are distinguished from non-stem cells because they have the property of

Self-renewal

Their primary role is to maintain and repair the tissue in which they are found

Adult stem cells

In bone marrow, two populations of adult stem cells have been identified. What are they?

1. ) Hematopoetic stem cells | 2. ) Stromal stem cells

Forms all of the types of blood cells in the body

Hematopoetic stem cells

Form bone, cartilage, fat, and connective tissue

Stromal stem cells

Obtained from the inner cell mass of 4-5 day old blastocysts

Embryonic stem cells

Can be cultured in vitro so that they are either prevented from differentiating or they are forced to differentiate

Embryonic Stem Cells

In order to culture ES cells, ICM cells are plated onto a layer of -provide source of growth and attachment

Mouse fibroblast feeder cells

To culture ES stem cells in vitro and prevent them from differentiating, ICM cells are plated with factors that inhibit differentiation such as

Leukemia inhibitory factor (LIF)

LIF binds to a heterodimer composed of LIF receptor and gp130, which activates

JAK/Stat3 signalling

The activation of JAK/Stat3 signaling effectively blockes the

MAPK pathway (and thus differentiation)

Typically, hematopoetic stem cells (HSCs) from long bones, hips, and spine are isolated using a method called

Multi-parameter flow cytometry

We can identify stem cells using cell surface markers directed against specific

Membrane receptors

The most common method of isolating stem cells is

Fluorescence-activated cell sorting (FACS)

How are adult and embryonic stem cells stimulated to differentiate in vitro?

1. ) Change chemical composition of medium 2. ) Alter surface of culture dish 3. ) Introduction of certain genes

Gene expression must be maintained for a differentiated cell to remain committed to a specific

Phenotype

To maintain gene expression, the transcription factor whose gene is activated can bind the

Enhancer of its own gene

To maintain gene expression, we synthesize proteins that act on chromatin to keep the gene

Accessible

If differentiation is dependent on a particular signaling molecule, the cell can make both the molecule and its receptor to maintain

Gene expression

Cells can interact with one another to stimulate eachother to remain

Differentiated

What are the five ways of obtaining human pluripotent stem cells?

1. ) from Morula (before 16 cells) 2. ) from ICM of blastocyst 3. ) from primordial germ cells of a fetus 4. ) from adult 5. ) through somatic nuclear transfer

There are 24 candidate genes for pluripotency factors that can be used to make iPS cells, what are 4?

1. ) Oct4 2. ) Sox2 3. ) Klf4 4. ) cMyc

One of the challenges to reprogramming is that we have to perform genomic insertion and inserted genes can insert

Mutations

Creates the potential for tumors because it is an oncogene

cMyc

Formed in 2012 to build a collection of iPS cell lines for drug screening for a variety of disease

StemBANCC

A "human liver" was synthesized using which stem cells?

Hepatocytes, endothelial stem cells, and mesenchymal stem cells

In medical research, iPS cells have been used for

Disease modeling and drug development, organ synthesis, and tissue repair

Tumors arise from cells termed cancer stem cells that have properties of normal stem cells, particularly

Self-renewal and Multipotency

Unregulated cell growth is due to a disruption in the regulatory mechanism in

Stem cell renewal

A stem cell disorder, and not a simple mechanism whereby cell proliferation is disrupted

Cancer

One problem with cancer treatment is that stem cells divide slowly, giving themselves plenty of time to repair any damage caused by

Radio- or chemotherapy

Stem cells retain the essential property of self-protection through the activity of

Multiple drug resistance transporters

Thus, a mutation that allows for unbridled cell growth will render chemotherapy

Ineffective

Conventional chemotherapies kill the bulk of the tumor but do not eliminate the

Cancer stem cells giving rise to it

Tend to be chemoresistant

Stem cells

The most common primary brain tumor with a median survival of about 1 year

Glioblastoma

This poor prognosis is due to therapeutic resistance to

Temozolomide