Opavsky - Stem Cells

what are stem cells

cells with potential to develop into many cell types

why do stem cells self-renew

to maintain the SC pool

why do stem cells differentiate

to replace dead/damaged cells

what are some properties of stem cells

plasticity, self renewal, differentiation potential, lack of specialization

what ensures that the SC pool is constant by giving rise to 2 identical SC daughter cells

symmetric cell division

what produces 2 daughter cells that are different - one being a SC and one a progenitor cell

asymmetric cell division

what are progenitor cells

SC that undergo additional cell division until they are mature specialized cells

which asymmetric division is dependent on the amount of cell-fate determinant that is placed in each daughter cell

intrinsic

which asymmetric division is dependent on interactions with neighboring cells & its environment

extrinsic

what are the types of stem cells

embryonic, somatic, primordial, induced-pluripotent

which SC is limited in number & enables healing, growth, & replacement of cells lost within a specific tissue

somatic

what is the microenvironment that provides support & signals self renewal or differentiation to SC

niche

how can SC receive signals for self-renewal or differentiation

niche can be through direct contact, soluble factor, or intermediate cells

what are the core transcription factors within stem cells

Oct4, Sox2, Nanog

how do Oct4, Sox2, and Nanog impact stem cells

activate transcription & contribute to the poised state of lineage-specific genes (differentiation)

what are the stages of differentiation

1. inactivation of pluripotent genes & activation of specific genes

2. express transcription factors that control cell fate

3. initiation of proliferation & formation of specificity

4. maturation of cells = functionality

what are the factors that aid differentiation

genetic, epigenetic, regulatory

how do genetic factors aid in differentiation

expression of specific transcription factors & signaling molecules

how do epigenetic factors aid in differentiation

DNA methylation, histone modification, and noncoding RNA expression

how do regulatory factors impact differentiation

promotors & enhancers on the genome

what are promoters

noncoding DNA fragments that help initiate gene expression

what are bivalent promoters

marked with histone modifications for activation/inactivation to aid in pluripotency in embryonic SC

what are enhancers

noncoding DNA fragments that amplify gene expression

what are pioneer factors

transcription factors that can open a closed chromatin to activate gene expression by binding to closed chromatin (requires other TF to activate enhancers)

what are master regulators

transcription factors that regulate cell fate & lineage commitment in development