Stem Cells Flashcards

1
Q

What Properties Define Stem Cells?

A
  • unspecialized (undifferentiated)
  • can self-renew
  • can be induced to differentiate into cells with special functions.
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2
Q

Asymmetric stem cell division:

A
  • predominates under steady-state conditions.
  • serves to maintain a balance between differentiated and undifferentiated cells.
  • Gives rise to one stem cell and one cell that will differentiate.
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3
Q

Symmetric stem cell division:

A
  • predominates when stem cells must expand in number, such as during development or after injury.
  • Gives rise to two identical stem cells.
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4
Q

Asymmetric Division may be due to (2):

A
  • asymmetrical segregation of “steaminess” factors.
  • one cell placed in different microenvironment and differentiates.
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5
Q

What are two ways to keep stem cells in an undifferentiated state intrinsically?

A
  • transcription factors
  • DNA-binding proteins
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6
Q

What transcription factors negatively regulate the expression of differentiation-promoting genes?

A
  • Sox2
  • Oct4
  • Nanog
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7
Q

What DNA-binding protein suppresses transcription of differentiation-inducing genes such as GATA4 and
GATA6?

A

Ronin

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8
Q

What molecules can extrinsically block stem cell differentiation and what are their pathways?

A
  • LIF works through STAT3 pathway
  • BMP work through SMAD-Id pathway

BOTH BLOCK MAPK PATHWAY

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9
Q

What is the stem cell niche?

A
  • the microenvironment in which stem cells reside in their undifferentiated state.
    • a chemical and/or mechanical environment
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10
Q

The intestinal crypt niche:

A
  • Intestinal crypt stem cells give rise to TA cells that can differentiate into all cell types required in the vili and also to Paneth cells.
  • Paneth cells remain in close proximity to the stem cells
    • stem cells will not divide if Paneth cells are removed
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11
Q

The three types of stem cells:

A
  1. Adult stem cells
  2. Embryonic stem cells
  3. Cancer stem cells (CSCs)
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12
Q

Embryonic stem cells:

A
  • Undifferentiated cells derived from a 5-day preimplantation embryo
  • pluripotent
    • have potential to differentiate into a wide variety of specialized cell types.
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13
Q

Cancer stem cells (CSCs):

A
  • Cells that drive tumorigenesis and also give rise to differentiated progeny.
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14
Q

Adult stem cells:

A
  1. undifferentiated cells found in a differentiated tissue
    • can self-renew and differentiate into all the specialized cell types of the tissue from which it originated.
  2. induced pluripotent stem cells
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15
Q

Differentiated Cells:

A
  • a cell that through the process of differentiation has acquired specialized structure and function.
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16
Q

Differentiated Cancer Cells:

A
  • cells are mature
  • look like cells in the tissue from which it arose
17
Q

Undifferentiated Cells:

A
  • a cell that has not yet acquired a special structure or function.
18
Q

Undifferentiated Cancer Cells:

A
  • cells are very immature and “primitive”
  • do not look like cells in the tissue from which it arose
19
Q

Dedifferentiation:

A
  • A process by which a partially or terminally differentiated cell reverts to an earlier developmental stage.
    • Directed reprogramming of such cells could be a powerful tool for tissue engineering.
20
Q

Totipotent Cells:

A
  • stem cells that are produced from the fusion of an egg and sperm as well as from the first few divisions.
  • can give rise to embryonic and extraembryonic tissues.
21
Q

Pluripotent Cells:

A
  • descendants of totipotent cells that can differentiate into cells from any of the three germ layers-ectoderm, endoderm, or mesoderm.
  • ICM cells are pluripotent potency.
22
Q

Multipotent Cells:

A
  • stem cells that can differentiate into a number of cells, but only those of a closely related family of cells.
    • Example: hematopoetic stem cells
23
Q

Oligopotent Cells:

A
  • stem cells that can differentiate into only a few cells, such as lymphoid or myeloid stem cells.
24
Q

Totipotent cells are produced from what event?

A
  • the fusion of an egg and sperm as well as from the first few divisions.
25
Q

Inner cell mass (ICM) cells are wht kind of stem cells?

A

pluripotent

26
Q

Unipotent Cells:

A
  • Cells that can produce only one cell type, their own.
  • Have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells).
27
Q

The primary role of adult stem cells is:

A
  • to maintain and repair the tissue in which they are found.
28
Q

How can stem cells be maintained in vitro?

A
  1. plate them onto a layer of mouse fibroblast feeder cells.
  2. plate them into a tissue culture medium containing leukemia inhibitory factor (LIF)
29
Q

How does LIF function to maintain stem cells?

A
  • binds to a heterodimer composed of LIF receptor and gp130 which activates JAK/Stat3 signaling.
    • blocks the MAPK pathway to prevent differentiation.
30
Q

How are stem cells identified in tissue?

A
  • by using cell surface markers directed against specific membrane receptors only found on stem cells.
    • receptor “fingerprints”
31
Q

How are stem cells isolated?

A
  • most common is fluorescence-activated cell sorting (FACS) based on surface receptor tagging.
    • a form of flow cytometry
32
Q

Cell differentiation is largely due to:

A
  • highly-controlled modifications in gene expression.
33
Q

Three ways adult and embryonic stem cells can be stimulated to differentiate:

A
  1. change chemical composition of culture medium.
  2. alter surface of culture dish.
  3. introduce genes into the stem cells.
34
Q

4 ways nature has developed to maintain the differentiated state of cells:

A
  1. transcription factor can bind to enhancer of its own gene.
  2. Proteins act on chromatin to keep the gene accessible.
  3. Cell can make both the signaling molecule and receptor if differentiation is signaling dependent.
  4. Cells can interact with neighboring cells such that each one stimulates the other to remain differentiated.
35
Q

What is the new theory underlying cancer?

A
  • Cancer is a stem cell disorder and not a simple mechanism whereby cell proliferation is disrupted.
  • Tumors arise from cells termed cancer stem cells that have properties of normal stem cells, particularly self-renewal and multipotency.
36
Q

What likely causes relapse and metastasis of cancer?

A
  • Cancer stem cells that persist in tumors as a distinct population.
  • Underlies difficulty in treating some cancers.
37
Q

What process is thought to protect cancer stem cells from radiation and chemotherapy?

A
  • self-renewal
    • radiation and chemotherapy may only be targeting the differentiated tumor cells, and not the CSC population of the tumor.
38
Q

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

A
  • CSCs divide slowly.
    • Conventional chemo/radiotherapy targets rapidly dividing cells. Gives time to repair before next division.
  • CSCs have multiple drug resistance transporters.
  • CSCs are in low frequency in the tumor.