cellular differentiation and stem cells

cell differentiation

process by which a less specialized cell becomes a more specialized cell type

all the cells arise from a single fertilized egg, contains the same DNA in their nuclei but become different to each other to form the various structures, tissues and organs and carry out their functions

control of cellular differentiation

all cells contain the same DNA but not all genes expressed in all cells

differential gene expression: cells become different because they express different genes

during development different cell types follow different differentiation programs

occurs in adults as well: adult stem cells divide and create fully differentiated daughter cells during tissue repair and normal cell turnover

stem cells

undifferentiated cells that divide and give rise to cells that differentiate into specialized cells

self renewal - maintains the stem cell pool

differentiating - replaces dead or damaged cells throughout your life e.g. muscle cell, nerve cell. cannot divide or make copies of itself

stem cell niches

microenvironment around stem cells that provides support and the signals that regulate self renewal and differentiation

direct contact - between niche and the stem cell

soluble factors - secreted by niche cell to act on the stem cell

intermediate cell - signal from the niche that acts on an intermediate cell which then acts on stem cell or secrete soluble factors

sources of stem cells

1. embryonic stem cells

2. tissue stem cells

3. induced pluripotent stem cells

stem cell terminology

multipotent - can make multiple types of specialized cells, but not all types. tissue cells are multipotent

pluripotent - can make all types of specialized cells in the body. lack potential to contribute to extraembryonic tissue such as placenta. embryonic stem cells from ICM are pluripotent

totipotent - can make all types of cells plus cells that are only needed during development of the embryo e.g. placenta, umbilical cord. early embryonic cells are totipotent

embryonic stem cells

found inf the blastocyst (very early embryo)

embryonic stem cells taken from the inner cell mass of the blastocyst and are cultured in a lab to grow more

through differentiation they can make all possible types of specialized cells, depending on the conditions they are grown under

tissue stem cells

can be found in the surface of the eye, brain, skin, breast, intestines, testicles, bone marrow and muscles

through differentiation the blood stem cell found in bone marrow makes only specialized types of blood cells: red blood cells, white blood cells, platelets.

multipotent: tissue stem cells can only give rise to the kinds of cell found in the tissue they belong to

principles of renewing tissues

stem cell: self renewal, divide rarely, higher potency, rare → committed progenitors: transient amplifying cells, multipotent, divide rapidly, no self renewal → specialized cells: do work, do not divide

hematopoietic stem cells: HSC → committed progenitors (many) → specialized cells (T cell, B cell, dendritic cell, erythrocytes etc.)

mesenchymal stem cells: MSC → committed progenitors (small amount) → specialized cells (bone(osteoblasts), cartilage(chondrocytes), fat(adipocytes))

induced pluripotent (IPS) stem cells

behaves like an embryonic cell

genetic reprogramming = add certain genes to the cell

advantage: no need for embryos, genetically identical

disadvantages: large number of somatic cells needed long term studies still required

reproductive cloning

live birth cloning. Use to make two identical individuals. Illegal on humans

take the cell containing DNA from the original subject. take a separate egg and remove the nucleus and take the rest of the cell and combine the two

somatic cell transfer

lab technique used for creating a clone embryo with a donor nucleus

important where there is a high probability of offspring having a genetic disease

therapeutic cloning

experimental cloning. Use to make patient specific cell lines isolated from an embryo (not intended for transfer in utero)

transfer of nuclear material from a somatic cell into an enucleated oocyte with the goal of deriving embryonic stem cell lines with the same genome as the nuclear donor

little to no risk of rejecting transplanted cells/tissues - immunology compatible with patient

ethical concerns and technical challenges

applications of stem cells

regenerative medicine - potential to treat diseases by replacing cells which are irreversible lost or damaged, and for which there are currently no therapies e.g. parkinson’s disease, heart disease etc. Bone marrow transplants and skin grafting are established examples for therapeutic use of stem cells

drug testing and screening

study disease processes

regulation of stem cell research

legislation regarding use of ES cells varies around the globe. many countries, new cell lines can be created from spare embryos from fertility clinics with the consent from the donors. laws prohibit the creation of embryos for research

Ireland has no regulations on stem cell research