Chapter 5 Flashcards
What is a stem cell?
A cell with high potential that can develop into any cell type. It maintains its own identity while producing different committed cells through aysmmetrical division.
What is the lineage of adult stem cells?
Multipotent: Can self renew indefinitely. Can further divide. Could remain in body forever.
Committed: Fated to differentiate. Can self renew. Will further divide.
Progenitor (transit-amplifying): Will proliferate into differentiated cells, can self-renew.
Differentiated cells: self-explanatory. Specialized cells. Cannot self renew. Cannot divide further.
Is a zygote a stem cell?
Yes. It can self renew and generate differentiated cells.
What are the different potencies of stem cells?
Totipotent: can generate all the cell types of the embryo and extra-embryonic tissues
Pluripotent: Can generate all the cell types of the embryo
Multipotent: Can generate many cell types, tissue specific
Unipotent: Can generate one cell type, tissue specific
Embryonic or adult in origin!
How were stem cells discovered?
Mice were irradiated lethally. Those untreated died. Those given bone marrow from non-irradiated mice recovered and lived healthy lives afterwards: thus something in the bone marrow must have saved them. Mice with this transplanted bone marrow showed self-renewing spleen colonies that healthy mice did not have after 8-12 days.
What type of stem cells are hematopoietic stem cells?
Multipotent: give rise to a specific lineage of differentiated cells.
How many progenitors do hematopoietic stem cells produce? How many progenitors do these have in turn? What are their roles in the immune system?
Lymphoid progenitor: T and B lymphocytes and NK cells. Adaptive immune.
Myeloid progenitor: Neutrophil, basophil, eosinophil, monocytes, platelets, RBCs. Innate immune.
How are HSCs used in treating blood cancer?
- Blood is taken from a healthy donor and 2. processed to remove the stem cells. 3. The patient undergoes chemotherapy to kill the cancer and weaken immune system to lessen likelihood of rejection.
- Infused into patient.
How are intestinal cells regenerated?
Via the Wnt pathway.
What are the five key cell types of the small intestine epithelium and their roles?
- Enterocytes: absorption of fluids/nutrients
- Enteroendocrine cells: produce hormones for intestine function
- Goblet cells: secrete mucus
- Tuft cells: chemosensors/T-cell activators
- Paneth cells: produce antimicrobial molecules, maintain SCs by activating Wnt pathway (provide Wnt3a)
How was intestinal regeneration explored in vivo? In vitro?
LGR5+ in vivo was labelled with tdTomato+, the stem cells and their progeny was stained red.
LGR5+ in vitro was labelled with GFP+, the cells of the epithelium were isolated, each cell gave rise to organoids resembling crypts and villi.
What are some tissues and organs with adult somatic stem cells?
Blood, intestine, lungs, brain, skin, muscle, mesenchymal stem cells (in marrow), adipose tissues, heart
What is a model system for regeneration?
Planarian worms. Any part of the worm when cut will regenerate an entire worm. Only embryonic SCs can do this in humans.
What defines a cell’s type?
Shape and function which are driven by gene expression.
Give a basic overview of single-cell transcriptonomics and how it lets us find new cells.
Embryos have stem cells dissociated, a platform conducts genomics for many genes, similar cells cluster together which reveals different cell types, plotted by PCA or t-SNE (similar, just spreads the clumps for better visualization). Can label and identify these clusters and the degree of gene expression for each. Use markers too.
Why can’t humans regenerate like planarians?
We don’t produce pluripotent adult SCs. Only embryonic.
Where can you find pluripotent embryonic stem cells?
From blastomeres of the inner cell mass. Oct4 specifically is a marker of pluripotency required for it, KO results in death. The two major sources of these blastomeres are the inner cell mass and primordial germ cells.
What happens if you put pluripotent stem cells in a media that promotes differentiation in vitro? In vivo?
Teratomas. They have all 3 germ layers. It’s characteristic of pluripotent stem cells.
What aspects of stem cell pools are finely regulated?
Maintenance, rate of proliferation and self-renewal, differentiation of stem cell progeny.
What are the main modes of stem cell regulation?
Extra-cellular:
Physical: Ex: Hippo mechanosensor
Chemical: Endocrine, paracrine (Wnt), juxtacrine (Notch)
Intracellular:
Cytoplasmic: Notch
* Asymmetric: Hippo
* Symmetric: B-catenin destruction complex
Transcriptional: Smads, B-catenin, YAP/Taz
Epigenetic: DNA accessibility b/w stem cells and progeny
What is the role of the Hippo Pathway in Inner Cell Mass (ICM) formation?
It signals asymmetrical signalling from the basal surface of the pre-trophectoderm leading to the division of a cell which becomes the ICM.
This occurs because the Hippo pathway is linked to the expression of apical proteins in the trophectoderm called PAR (Partitioning defective) and aPKC (atypical protein kinase C) which associate with each other and angiomotin and inhibit it, allowing transcription in this cell.
In the ICM cell adhered through E-cadherin to the trophectoderm, this causes a hippo kinase cascade which signals degradation of LATS1/2 which inhibits Yap/Taz which inhibits the Wnt/B-catenin pathway and the TGF-Beta/BMP SMADS pathway which allows Oct 4 activity. This inhibition is necessary for the further propagation of the ICM to form primordial germ cells, a loss of Oct4 leads to epiblast formation.
What are the three factors of Inner Cell Mass formation?
Apical base polarity, Asymmetrical Hippo signalling activation, Asymmetrical cell division
What is the role of Notch signalling in adult stem cells?
From Intestinal stem cells, enteroblasts are formed. If Notch is activated, further differentiation of the EBs occurs to enterocytes, if it is inhibited, the EBs differentiate to enteroendocrine (secretory) cells.
If Notch is KO’d, asymmetrical cell division stops and it causes tumor-like conditions because of a lack of differentiation
What is a stem cell niche?
The micro-environment that houses stem cells, protects their pool and controls their self-renewal. This can involve Notch and Wnt and Delta ligands in the intestine, for example, to maintain SC regeneration, otherwise they can lose their identity.
