Part 3 Flashcards
Organogenesis
the process of organ formation.
Early organogenesis is a symphony of interactions between different parts of the embryo, and some of these create privileged sites called stem cell niches.
Stem cell niches
provide a milieu of extracellular matrices, juxtacrine factors, and paracrine factors that allow cells residing within them to remain relatively undifferentiated. => Stem cells.
Stem cell definition:
A relatively undifferentiated cell that when it divides produces:
- At least one of two daughter cells that retains its undifferentiated character (self-renewal)
- A daughter cell that can undergo further differentiation.
Single stem cell asymmetry mode
seen in many types of stem cells, strategy in which two types of cells (self-renewal + developmentally committed cell) are produced at each division.
Population asymmetry mode
an alternative (but not mutually exclusive) mode of retaining cell homeostasis, where some stem cells are more prone to produce differentiated progeny, and this is compensated for by another set of stem cells that divide symmetrically to produce more stem cells.
Multipotent stem cells
progeny include another multipotent and one committed to a particular cell lineage (single asymmetry mode).
Committed stem cells
progeny of multipotent, produces other committed stem cells + a progenitor cell (aka transit amplifying cells)
Progenitor cells (Transit amplifying cells)
are committed to a particular cell fate and divide to produce many such cells. (Not really a stem cell, as they can only undergo a few rounds of cell division). Transit amplifying, pga usually divide while migrating away from the stem cell niche.
Subpopulations of stem cells, found in several organs, fx adult bone marrow:
In some organs, fx gut, epidermis, and bone marrow, stem cells divide regularly to replace worn-out cells and repair damage.
In others, fx prostate and heart, division only occur under special physiological conditions, usually stress or repair.
The two major divisions of stem cells (based on their sources)
- Embryonic stem cells – derived from the inner cell mass of mammalian blastocysts, or from fetal gamete progenitor cells. Capable of producing all the cells of the embryo.
- Adult stem cells – found in the tissues of organs after the organ has matured. Can form only a subset of cell types.
Stem cell potency
the ability of a particular stem cell to generate numerous different types of differentiated cells.
Totipotent
capable of forming every cell in the embryo + the trophoblast cells of the placenta (in mammals).
Pluripotent
can become all the cell types of the embryo, but cannot generate the trophoblast. Usually derived from the ICM of the mammalian blastocyst, however, also from undifferentiated germ cells.
Multipotent stem cells
commitment is limited to a relatively small subset of all the possible cells of the body, i.e. the hematopoietic stem cell, found in both embryo and adult
Unipotent stem cells
found in particular tissues, involved in regenerating a particular type of cell, fx spermatogonia
Committed stem cells
common group for multipotent and unipotent stem cells, as they are limited in their potential.
Lineage-restricted cells
name for both unipotent stem cells and progenitor cells, even though only unipotent are self-renewing
Precursor cell
widely used inn developmental biology to denote any ancestral cell type (either stem cell / progenitor cell) of a particular lineage, most often when the distinction between do not matter or are not known.
Adult stem cells
Numerous adult organs contain stem cells that can give sire to a limited set of cell and tissue types, fx epidermis, hair, melanocyte, tooth etc.
Difficult to isolate though, pga fewer they are 1:1000 cells in an organ.
In addition, low cell division rate (do not proliferate readily).
Hematopoietic multipotent stem cells: 1:15000 bone marrow cells
Stem cell niches
regulatory microenvironment that houses the continuously proliferating stem cells. Allows the controlled self-renewal of stem cells and the controlled differentiation of the progeny that leaves the niche.
Stem cell niche microenvironments usually regulate via paracrine / juxtacrine factors produced by the cells that make up the niche.
In many cases they keep stem cells uncommitted, once they leave, no longer able to => differentiation.
Too much proliferation =>
risk of cancers
Balance regulated by antagonistic paracrine factors.
Mesenchymal stem cells: multipotent adult stem cells
Their potency remains a controversial subject, but they appear to have a surprisingly large degree of plasticity (compared to fx hematopoietic stem cells (limited to blood cells).
Found in several tissues, fx bone marrow, fat, muscle etc.
Differentiation of mesenchymal stem cells (MSCs) is predicated on both paracrine factors and cell matrix molecules in the stem cell niche.
They’ve been linked to normal growth and repair conditions in the human body.
Loss of MSC ability to differentiate may be a component of the normal aging syndrome.
May also produce paracrine factors that aid other, more specific stem cells to divide and repair tissues.
Pluripotent embryonic stem cells
Placing ESCs into media containing different paracrine factors they can be directed into particular paths of differentiation
Two major problems using human ESCs therapeutically:
- The transplanted ES cells come from another individual and thus are not the same genotype as the patient; ES cells can be rejected by the patient’s immune system. (Brain and eyes among the few places where immune rejection is not a big problem, brain pga blood-brain barrier shields it from the immune system).
- The several social and ethical issues raised by the fact that the ES cells are taken from human embryos.
Both problems can theoretically be circumvented by transforming somatic cells into pluripotent cells.
Induced pluripotent stem cell (iPS cell)
an adult cell that has been changed into a pluripotent cell. Opens up for ability to repair damaged organs
Natural stem cell therapy:
Pluripotent and multipotent stem cells have been found in the blood of pregnant mice and women. It appears that stem cells from the foetus enter the maternal circulation.
In humans, these cells leave the mother’s blood and integrate into her existing organs. They may also preferentially integrate into any damaged or diseased organs in the mother.
These fetal stem cells can be seen decades after the pregnancy.
It is possible that this happens to help the mother during pregnancy and the immediate stresses of labour and delivery.
