L15 – STEM CELLS 101

During embryogenesis, cells become more specialized/restricted in their developmental capacity.

Determination and Differentiation result not from changes in genes, but in gene expression (how the gene is read out in different individuals), with the exception of the immune system and gametes.
Changes in gene expression  alterations in chromatin structure and transcription factor expression.
Determination and differentiation often quite permanent and heritable through many cell divisions.

Determination of line specificity, a heritable change in a cell’s developmental line. Then differentiation occurs, resulting in changes in gene expression for its function in a particular tissue.

Transdifferentiation or de-differentiation when cells normally committed to one lineage, switches to a different lineage pathway. It can be artificially induced by ectopic expression within a cell of master regulator transcription factor  aids differentiation.

Trans-differentiation is quite common in a number of disease states such as :
Intestinal metaplasia of the eosophagus.
Damage to eosophageal epithelium through acid reflux  conversion of squamous epithelium into intestine. Precursor to esophageal adenocarcinoma.
Squamous metaplasia in the respiratory tract/bladder.

Developmental Capacity:
A multipotent cell gives rise to several types of mature cell.
A pluripotent cell gives rise to all types of adult tissue cells + embryonic tissue.
A totipotent cell can give rise to a new individual.

Adult tissues can have three states of renewal:
Continuously renewing: bone marrow, skin, gut.
Conditionally renewing: liver, kidney.
*normally quiescent during adult life, but when damage – can have substantial regeneration.
Non renewing: cardiac muscle