Stem Cells and Development

Stem cells, development, and metastasis

Terminally differentiated

cells that are in their final form; do not divide

most body cells are

Terminally differentiated cells are in __

G0

G0 phase

outside cell cycle; no longer progressing through cell cycle or dividing

senescent

permanently in G0; never dividing again

Examples of terminally differentiated cells

muscle, skin, brain, immune

Stem cells

unspecialized cells that divide to replicate/replace themselves and also to differentiate into many specialized cell types

All blood cells are derived from stem cells in ___

bone marrow

Two types of stem cells

embryonic vs. adult

Embryonic stem cells

come from embryos; need to be able to make the whole body/part of it; totipotent and pluripotent

totipotent

can differentiate into every cell type of the body

pluripotent

can differentiate into every cell type but not embryonic tissues

Adult stem cells

found in specific parts of the body, only can replace specific sets of cells

unipotent, multipotent, or pluripotent

unipotent

can only differentiate into one cell type

multipotent

can differentiate into multiple cell types within same group/lineage

examples of adult stem cells

bone marrow contains hematopoietic stem cells → produce blood cells

Stem cell research

use of cultured pluripotent stem cells to:

• identify drug targets and test potential therapeutics

• toxicity testing

• use as tissues/cells for transplants

• study cell differentiation → understand prevention/treatment of birth defects

Master transcription factors

gene that sits at top of gene regulation hierarchy; activates many genes related to that behavior

Specific transcription factors present in (embryonic/adult) stem cells maintain pluripotency

embryonic

Induced Pluripotent Stem Cells (iPSCs)

adding transcription factors active in stem cells to reprogram somatic cells to be pluripotent stem cells; forced activation of master transcription factors

How can iPSCs be used to treat cancer patients?

make patient-specific iPSC by reprogramming pt’s cells to IPSCs → now they can differentiate into healthy cells that are already specific to that pt

Steps of using iPSCs to treat cancer patients

1. make patient-specific iPSCs (in dish)

2. use gene targeting to repair disease-causing mutation

3. in vitro differentiation of repaired iPSC → healthy cells

4. genetically-matched (pt-specific) healthy cells are transplanted to patient

differentiation

cell specialization (ex. liver cells, intestinal cells, cardiac cells, blood cells, nerve cells, muscle cells)

Different transcription factors lead to differences in ___ and ___

differences in gene expression and differentiation

What accounts for differences in gene expression?

cell signaling and cell memory

How does combinational signaling (two cell signals released at same time) affect gene expression?

different combinations produce different gene expression, leading to different responses in cells

How does cell memory affect gene expression?

same type of cells receive different signals first, then receive same signal later → will have different responses

Signaling molecule gradients

how much signal a cell is exposed to; affects differentiation

Cellular response to signaling molecule gradient

differs across gradient due to various concentration of signal

metastasis

spread of cancer to secondary location

Malignant tumors

form secondary tumors, aka metastases

steps of metastatic progression

1. invasion

2. intravasation

3. circulation

4. extravasation

5. pre-metastatic niche

6. micrometastasis

7. colonization at target organ

invasion

going outside original location of tumor

intravasation

getting into circulatory system

circulation

circulating through circulatory system to travel to secondary location

extravasation

get out of circulatory system

pre-metastatic niche

micrometastasis

small clusters of cancer cells that have metastasized to secondary location

colonization

metastasized cancer cells grow into new tumor at distant/secondary organ/location

Epithelial-Mesenchymal Transition (EMT)

generates migratory stem cells; stationary, epithelial cells transition to migratory, mesenchymal cells

EMT relation to metastasis

EMT is wrongly activated in early metastasis, explaining how cancer cells travel (epithelial cells will become mesenchymal cells and migrate out of original location)

some EMT signals and markers (master regulators)

Twist, Snail, SIP1

in situ

in place