Stem cells Flashcards
Stem Cell
Cells that have the ability to self renew and to give rise to cells that can differentiate.
Totipotent
Least determined, capable of giving rise to any cell type
Pluripotent
Capable of giving rise to many cells types
Multipotent
Make more than one cell type in a closely related family
Unipotent
Produce one differentiated cell type
Progenitor cells
Can differentiate into multiple cell types, but can only renew a limited number of times. Transient
Stem cell
Can divide indefinitely and generate specified cells
ES cells
Embryonic Stem Cells
Pluripotent
ICM derived
Adult Stem Cells
Multipotent cells Found in adult tissues, thought to be involved in maintaining tissue homeostasis of providing cells for naturally regenerative organs (skin, blood, hair…)
Induced Pluripotent stem cells (iPSCs)
Adult cells that have been converted to cells with the pluripotency of embryonic stem cells
Stem cell niche hypothesis
A special microenvironment regulates stem cell self-renewal and survival and the differentiation of the progeny that leave the niche.
Stem cell niche hypothesis
Signaling factors
Keep cells alive and in multipotent state
Stem cell niche hypothesis
Adherence factors
Keep cells in the microenvironment
Stem cell niche hypothesis
Asymmetric Division
Positions daughter cells with respect to niche
Fly ovarian stem cell niche
Adherence factor
E-cadherin keeps 1 daughter cell in niche
Fly ovarian stem cell niche
ECM
Acts as a localized signal
Extracellular matrix molecules keep BMPs close to the source
Fly ovarian stem cell niche
Cap cells
Cap cells secrete Bone Morphogenic Proteins (BMPs) that bind to receptors on the surface of GSCs.
BMP signal is sent to GSC nucleus
Bam is repressed - differentiation is prevented
Fly ovarian stem cell niche
GSCs
Germline stem cells are in a niche at the tip of each ovariole, where they are in direct contact with cap cells.
Fly ovarian stem cell niche
Mitotic spindle
The cell divides perpendicular to the stem cells so that one cell receives signals to retain identity while the other is displaced.
Fly ovarian stem cell niche
BAM LOF mutation
With no bam, there is no renewal and there is a bag of marbles mutation.
Small intestinal epithelium
Crypt base
Crypts contain intestinal stem cells that produce new cells to replace the old cells in villi.
Crypt base contains ISCs called CBCCs
Small intestinal epithelium
Transition amplifying zone
Expands pool of cells created by ISCs to ensure a sufficient supply of differentiated cells
Small intestinal epithelium
Intestinal lumen - paneth cells
Paneth cells secrete EGF and Wnt 3a to regulate CBCC symmetrical division.
Small intestinal epithelium
Stroma signaling
The stroma has a gradient Wnt 2b and R-spondin which is necessary for the survival and. proliferation of CBCCs
CBCCs
crypt base columnar cells
Characterized by Lgr5
Paneth cell
Secrete Wnt 3a and R-spondin which stimulates the proliferation of CBCCs
Wnt/ BMP gradient
WNT - strong at the base of the crypt, maintains stem cell populations (Wnt 2b, respondin, noggin)
BMP - Highest in villi region, important for differentiation.
Cre system
Cre: bacteriophage that has a recombinase which recognizes lox sites
Lox: Unique 34 bp DNA sequence that gets removed by Cre
Tests of Stemness
- iPSCs can differentiate in vitro
- Teratoma Asso in vivo
- Mouse embryo cimera
Induced pluripotency
IPSCs
Differentiated cells can revert to a more plastic state
Using viral vectors to revert potency
First demonstration of potency reversal
Takahashi/Yamanaka
1. compiled a list of pluripotency factors
- factors that promote pluripotency : Oct4, Sox2, Nanog
2. Made skin cells with an Fbx15p:b-georeporter and infected cells with pools of the factors.
Fbx15 : B-georeporter
Fbx15: on in embryo and ES, off in differentiated cells
B-geo: blue reporter
Reporter fusion approach
Finding blue cells after infecting cells with pools of viruses expressing pluripotency factors
Organoid
3D tissue structures generated from iPSCs, which self-organize in vitro and exhibit some of the key features of eh represented organ
