Stem Cells (Foty)

Question 1

What 2 properties define stem cells

Answer 1

1) they are unspecialized (undifferentiated) and can self-renew
2) they can be induced to differentiate (into cells with special functions

Question 2

2 types of self-renewal are

Answer 2

1) asymmetric division

2) symmetric division

Question 3

Asymmetric division predominates under__________ conditions

It’s purpose is to:

Answer 3

Asymmetric division predominates under steady-state conditions

It serves to maintain a balance between differentiated & undifferentiated cells

There is an asymmetrical segregation of factors that promote “stemless” to one daughter cell & not the others

Aka one cell stays within the “niche” microenvironment & remains undifferentiated while the other is displaced from the niche and differentiates.

Question 4

Symmetric divisions predominate when _______

Answer 4

When stem cells must expand in number such as during development or after injury

Question 5

Cell-intrinsic regulation of Stem Cell Self-renewal include _______ transcription factors

These ____regulate expression of differentiation-inducing genes

There is also a DNA binding protein ____ which does what?

Answer 5

Sox2-Oct4-Nanog

NEGATIVELY regulate expression of differentiation-promoting genes

DNA-binding protein Ronin suppresses transcription of differentiation-inducing genes: GATA4 & GATA6

Question 6

Cell-extrinsic regulation

Answer 6

LIF, BMP work through STAT3, SMAD-Id to block MAPK pathway

Question 7

The stem cell niche describes_____

What specifies it?

Answer 7

The microenvironment in which stem cells reside in their undifferentiated cells

Cell0cell, cell-substratum interactions, growth factors, cytokines etc specify the niche environment

Question 8

What results in a re-specification of the niche environment?

Answer 8

Tissue injury –> this can result in increased proliferation & differentiation

Ex: cancer can re-specify the niche; when niche is re-specified, that can give rise to increased proliferation and differentiation

Ex: the intestinal crypt niche

Crypt cells give rise to TA cells that can differentiate into all the cell types (and paneth cells)

Paneth cells remain in close proximity to the stem cells; TA cells move up

Cells won’t divide when they’re by paneth cells

Question 9

Adult stem cells

Answer 9

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

Primary role: maintain & repair tissue in which they are found

Adult tissues that contain these: Brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, intestinal crypt, liver

Bone marrow: HSCs & Stromal stem cells (form bone, cartilage, fat, connective tissue)

Question 10

Induced pluripotent stem cells (iPSCs)

Answer 10

Pluripotent stem cells artificially derived from a non-pluripotent cell

Typically an adult somatic cell getting a forced expression of specific genes

Question 11

Embryonic stem cells

Answer 11

Undifferentiated cells derived from a 5-day preimplantation embryo (blastocyst) that have potential to differentiate into a wide variety of specialized cell types

Can be cultured in vitro under conditions that prevent them from differentiating Or to induce them to differentiate towards a particular phenotype

Question 12

Cancer stem cells

Answer 12

Cells that drive tumorigenesis and also give rise to differentiated progeny

Question 13

Dedifferentiation

Answer 13

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

Question 14

Totipotent

Answer 14

Stem cells produced from fusion of egg & sperm/a few divisions

Can give rise to embryonic & extra-embryonic tissues

Question 15

Pluripotent

Answer 15

Descendants of Totipotent cells that can differentiate into cells from any of 3 germ layers (ectoderm, endoderm, mesoderm)

ICM cells are pluripotent

Question 16

Multi potent

Answer 16

Stem cells can differentiate into a number of cells but only those of a closely related family of cells

Example: hematopoetic stem cells

Question 17

Oligopotent

Answer 17

Stem cells can differentiate into only a few cells

Lymphoid or myeloid stem cells

Question 18

Unipotent

Answer 18

Cells can produce only one cell type, their own, but have the property of self-renewal which distinguishes them from non=stem cells

(Muscle stem cells)

Question 19

How are stem cells cultured in vitro?

Answer 19

1. ICM cells plated onto a layer of mouse fibroblast feeder cells (these are inactivated, they provide a source of growth & attachment )
2. ICM cells can be plated onto tissue culture medium containing factors that inhibit differentiation (leukemia inhibitory factor)

• –> LIF binds to a heterodimer composed of LIF receptor & gp130
• –> this activates JAK/Stat3 signaling —>blocks the MAPK pathway to prevent differentiation

Question 20

How are stem cells identified?

Answer 20

Very rare

-use cell surface markers directed against specific membrane receptors

Question 21

How are stem cells isolated

Answer 21

Fluorescence-activating cell sorting (FACS)

Question 22

How are adult and embryonic stem cells stimulated to differentiate

Answer 22

1) changing the chemical composition of the culture medium
2) altering the surface of the culture dish
3) modifying the cells by introducing certain genes

Question 23

For a cell to remain committed to a particular phenotype what has to be maintained and what are the 4 ways of doing this?

Answer 23

Gene expression has to be maintains

1) Transcription factor whose gene is activated by signal transduction cascade can bind to enhancer of its own gene (positive feedback)
2) synthesizing proteins that act on chromatin to keep gene accessible
3) cell can make both molecule & receptor if differentiation dependent on a particular signaling molecule
4) cells can interact with neighboring cells s.t. Each one stimulates the other to remain differentiated

Question 24

What is regenerative medicine

Answer 24

Use of stem cells to repair or replace damaged tissues

Question 25

Cancer stem cell theory

Answer 25

• tumors arise from cancer stem cells; self-renew & Multipotent
• unregulated cell growth due to a disruption in regulatory mechanism in stem cell renewal
• cancer is a stem cell disorder
• CSCs persist in tumors as a distinct population..likely causes relapse and metastasis

Question 26

How does self-renewal protect CSCs from UV and chemotherapy?

Answer 26

• self-renewal by asymmetric division will generate population of differentiated cells & a population of cells w stem-like properties
• stem cells divide slowly; give time to repair damage; fast- dividing cells will die off
• retain property of self-protection thru drug resistance transporters (remains at low frequency among heterogenous tumors mass)
• conventional chemo kills bulk of tumor, not stem cell -> relapse
• stem cells also chemo resistant