Lecture 5 Tissue Renewal 1

Question 1

Two primary features of stem cells

Answer 1

Limitless self renewal

Developmental potency

Question 2

Transit amplifying cells

Committed progenitor cells

Answer 2

Limited lifespans

Divide rapidly to produce daughter cells that differentiate to generate and maintain tissues

Question 3

Totipotent

Answer 3

Zygote/first division blastomeres can make all tissues (embryonic and extra embryonic)

Question 4

Pluripotent

Answer 4

Can make all embryonic tissues but not placenta

Question 5

Multipotent

Answer 5

Can make multiple cell types in tissue

Question 6

Uni potent

Answer 6

Can make one type (spermatogonial stem cells)

Question 7

How can a stem cell divide to produce one stem cell and one committed progenitor?

Answer 7

Two models:
Divisional asymmetry (stemness segregate into one)
Environmental asymmetry (niche provides signals that help stem cells retain self renewal and pluripotency)

Question 8

How are adult stem cells identified?

Answer 8

Hematopoietic stem cells found in bone marrow in adults (yolk sac blood islands, fetal lived in developing embryos)
Self Renewand are Multipotent

Flow cytometry

Question 9

CD Antibodies

Answer 9

CD38 low CD34 high

Question 10

Functional assay for identification of stem cells

Answer 10

Adoptive transfer
-inject irradiated mice with BM cells
- can identify long term reconstituting (LTR) cells–HSCe
CD34+ CD38-

Question 11

Short term reconstituting cells

Answer 11

Committed progenitors can repopulate all lineages but only briefly as they lack permanent self renewal

Question 12

Mammary epithelial stem cells (Shackleton 2096)

Answer 12

Single mammary epithelial cell was objected into recipient mammary glands devoid of their own epithelium
Small percentage of these cells can reproduce the entire structure with multiple cell types

Question 13

Intestinal lining

Answer 13

Stem cells in the crypt villus junction that give rise to differentiated cells

Question 14

Epidermal stem cells

Answer 14

Inter follicular SCs produce rapidly dividing transit amplifying cells whose progeny differentiate into keratinocytes
In the hairshaft bulge– called label retaining cells (divide very rarely)

Question 15

Two models for stem cell and transit amplifying cell

Answer 15

Hierarchical model : rare divisions by stem cells generate rapidly dividing transit amplifying cells which give rise to differentiated cells
Stochastic model: all basal cells are the same and each division can yield three different outcomes

Question 16

Mesenchymal stem cells

Answer 16

Multipotent cells derived from a variety of tissues
When injected into the bloodstreamc they home to sites of SCs in damages tissues

CD105+ CD73+ CD45- CD19-
Can differentiate into osteoblasts, chondroblasts and adipocytes

Question 17

Induced pluripotent stem cells

Answer 17

Can convert differentiated fibroblasts into ES-like cells that self renew and pluripotent
Induced by transient expression of transcription factors (Oct4, Sox2, c-Myc, KLF4)

C-myc is an oncogene
KLF4 might drive tumor growth

Question 18

How can a cancer stem cell arise?

Answer 18

Option 1: transformation of a normal SC through mutations

Option 2: activation of self renewal in cancer cells– more evidence

Question 19

Evidence for activation of self renewal

Answer 19

Scott Armstrong introduced a specific ANL causing oncogene into normal committed mouse myeloid progenitor cell–caused AML
Induced self renewal correlates with changes in gene expression

Question 20

How can a cancer stem cell arise?

Answer 20

Option 1: transformation of a normal SC through mutations

Option 2: activation of self renewal in cancer cells– more evidence

Question 21

Evidence for activation of self renewal

Answer 21

Scott Armstrong introduced a specific ANL causing oncogene into normal committed mouse myeloid progenitor cell–caused AML
Induced self renewal correlates with changes in gene expression