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Stem Cells Week 10 Lecture Notes
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STEM CELL NICHEFeatures of a Stem Cell Niche (Schofield’s Idea)
- Restriction on stem cell entry into cell cycle and differentiation
programs.
- Integration of signals reflecting tissue and organismal state.
- Imposition of stem cell features on daughter cells.
- Mechanism for limiting “mutational errors”.
In the absence of niche signals,
adult stem cells will differentiate
by default
1. Self-renewal is proliferation
coupled to blocking
differentiation controlled by
signals.
2. Signals are local; niches have a limited capacity and cells compete for the signals.
3. The signals control tissue homeostasis, also damage.
Schematic Representation of the BMP Signalling Pathway
* Type I and type II BMP receptors span the cell membrane and bind
extracellular BMP ligand.
* Activates signaling through type II-receptor-mediated phosphorylation
of the type I receptor on the glycine-serine (GS) domain.
* Activated type I receptors phosphorylate cytoplasmic signal transduction
proteins such as RSMADs and MAPKs which regulate the transcription
of target genes in the nucleus.
Integration of Wnt and BMP Signals within the intestine
- LGR5+ crypt base columnar (CBC) stem cells intercalated with Paneth cells at the crypt base
- Stem cells continuously generate rapidly proliferating transit-amplifying (TA) cells
- TA cells differentiate into the various functional cells on the villi
- +4 ‘reserve’ stem cells can restore the LGR5+ CBC stem cell
compartment following injury
Hypoxia and Metabolism: Circadian control of tissue
homeostasis and adult stem cells
o Master circadian pacemaker driving rhythms is the suprachiasmatic
nuclei (SCN)
o SCN located in anterior hypothalamus
o Emerging evidence that deregulation of circadian rhythms impacts
peripheral tissues
, EMERGING AREAS OF RESEARCH
Designer matrices for intestinal stem cell and organoid
culture
High matrix stiffness significantly enhanced ISC expansion.
ISC differentiation and organoid formation, on the other hand,
required a soft matrix and laminin-based adhesion.
Fully defined culture system for the expansion of mouse and
human ISCs.
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