Lecture 24- stem cells and cell death

in multicellular organisms, most cells are what
mammalian skin

post-mitotic

multicellular organisms need to replace what cells to maintain tissues

Example: skin epidermis

damaged

stem cells can divide to make a second stem cell

(self-renew)

Symmetric cell division

divide to make a daughter that is different
(differentiate)

Asymmetric cell division

multicellular organisms need which cells to replace differentiated cells

stem

Adult stem cells often require which signals from a neighboring “niche” to stay stem cells

paracrine

stem cells divide how to maintain “stemness”

symmetrically

stem cells divide how to differentiate

asymmetrically

In intestinal crypt, which pathway regulates stem cell division

Wnt

multicellular organisms are made up of how many different cell

types – even though they come from one fertilized egg

many

number of cell types they can become

stem cell potency

can make any cell type

Totipotent

differentiate into all cell types except extraembryonic tissues

Pluripotent

reside in the inner cell mass of mammalian embryos

embryonic stem cells (ES cells)

Embryonic stem (ES) cells grow better in a dish than
differentiated cells, but require sacrificing what

embryo

ES cells can generate what in culture

organoids

harvested from the inner cell mass

Embryonic stem cells

harvested from adult tissues

Adult stem cells

-Ethical and legal issues
- Immune rejection
- Control of differentiation
- Tendency toward tumor formation

Against the use of Embryonic Stem Cells

- hard to identify and harvest
- slow to expand
- likely to pass on genetic defects
- do not have the capacity (totipotency)

Against the use of Adult Stem Cells

stem cells made in the lab

induced pluripotent stem cells (IPSCs)

can occur during development or in response environmental stress

apoptosis

occurs through a signal transduction cascade and is DISTINCT from traumatic death of a cell (necrosis or necroptosis)

apoptosis

clearance of apoptotic cells occurs by what

phagocytosis

apoptotic cells have characteristic high levels of
phosphatidylserine on the which membrane

outer

cysteine proteases required for apoptosis

caspases

executioner pro-caspases, cleaved to form active caspases

initiator caspases (cysteine-dependent aspartate-directed

proteases)

–protein kinases, some of which cause detachment of cells.

– Lamins, which line the nuclear envelope.

– proteins of the cytoskeleton

– Caspase-activated DNase (CAD)

executioner pro-caspases

bound TNF receptors recruit what to the intracellular domain of the receptor

procaspases

Procaspases convert other procaspases
to what

caspases

proapoptotic proteins like Bcl-2, Bax stimulate what to leak proteins, mostly cytochrome c

mitochondria

release of apoptotic mitochondrial proteins irreversibly commits the

cell to what

apoptosis

•Tumor necrosis factor (TNF) is detected
by a TNF cell surface receptor.
•bound TNF receptors recruit
“procaspases” to the intracellular
domain of the receptor.
•Procaspases convert other procaspases
to caspases.
•Caspases activate executioner
caspases, leading to apoptosis

extrinsic (receptor-mediated)

•activated by hypoxia, DNA damage, very
high Ca++, free radicals, etc
•proapoptotic proteins like Bcl-2,
Bax stimulate mitochondria to leak
proteins, mostly cytochrome c.
•release of apoptotic mitochondrial
proteins irreversibly commits the
cell to apoptosis

intrinsic (mitochondria-mediated)

p35 is an what inhibitor of Caspase 8

irreversible

p53 does or doesn’t affect Caspase 9

doesn’t

MC159 binds to the death effector domains of FADD, blocking the
binding sites for other what

proteins

differentiation of muscle cells

myogenesis