Extracellular matrix: A dynamic microenvironment for stem cell niche

Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis...

Wound Healing: A Cellular Perspective.

Senescence in Health and Disease

Detection of microbial DNA is an evolutionarily conserved mechanism that alerts the host immune system to mount a defense response to microbial infections. However, this detection mechanism also poses a challenge to the host as to how to distinguish foreign DNA from abundant self-DNA. Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is a DNA sensor that triggers innate immune responses through production of the second messenger cyclic GMP-AMP (cGAMP), which binds and activates the adaptor protein STING. However, cGAS can be activated by double-stranded DNA irrespective of the sequence, including self-DNA. Although how cGAS is normally kept inactive in cells is still not well understood, recent research has provided strong evidence that genomic DNA damage leads to cGAS activation to stimulate inflammatory responses. This review summarizes recent findings on how genomic instability and DNA damage trigger cGAS activation and how cGAS serves as a link from DNA damage to inflammation, cellular senescence, and cancer.

/pdf/the-cgas-cgamp-sting-pathway-connects-dna-damage-to-425b8zghb1.pdf

The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer.

The study of human genetic disorders and mutant mouse models has provided evidence that genome maintenance mechanisms, DNA damage signalling and metabolic regulation cooperate to drive the ageing process. In particular, age-associated telomere damage, diminution of telomere 'capping' function and associated p53 activation have emerged as prime instigators of a functional decline of tissue stem cells and of mitochondrial dysfunction that adversely affect renewal and bioenergetic support in diverse tissues. Constructing a model of how telomeres, stem cells and mitochondria interact with key molecules governing genome integrity, 'stemness' and metabolism provides a framework for how diverse factors contribute to ageing and age-related disorders.

/pdf/linking-functional-decline-of-telomeres-mitochondria-and-3yb672hnrg.pdf

Linking functional decline of telomeres, mitochondria and stem cells during ageing

https://www.cell.com/cell/pdf/S0092-8674(09)00374-2.pdf

Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells by Triggering Their Differentiation

https://www.cell.com/cell-stem-cell/pdf/S1934-5909(10)00651-X.pdf

Ken Inomata

Papers

Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells by Triggering Their Differentiation

Hair Follicle Stem Cells Provide a Functional Niche for Melanocyte Stem Cells