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Comparison of epithelial cells from various epithelia and hair follicle stem cells

ABSTRACT: The potency of an adult stem cell is restricted to certain lineages during embryonic life, in response to a specific microenvironment (the niche) and it is maintained for life. Lineage restriction is considered immutable. We have investigated if adult stem cells isolated from different epithelia could change fate by exposing them to a hairy skin niche. We have demonstrated that clonogenic stem cells restricted to a single epithelial lineage and cultured from various Tp63-expressing tissues e.g, the bladder, the vagina, or the thymus can acquire new functionality. When exposed to a hair skin microenvironment, these stem cells acquire the capacity to generate hair follicles and sebaceous glands, thus behaving like bona fide hairy skin multipotent stem cells. Genome wide-screen analysis has demonstrated that the stem cells express transcription factors typical of hair follicle differentiation, even though they continue to express some of the genes linked to their origin. This increase in potency demonstrates that lineage restriction is not immutable.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE116717 | GEO | 2020/09/17

REPOSITORIES: GEO

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Comparison of epithelial cells from various epithelia and hair follicle stem cells [microarray]

Project description:The potency of an adult stem cell is restricted to certain lineages during embryonic life, in response to a specific microenvironment (the niche) and it is maintained for life. Lineage restriction is considered immutable. We have investigated if adult stem cells isolated from different epithelia could change fate by exposing them to a hairy skin niche. We have demonstrated that clonogenic stem cells restricted to a single epithelial lineage and cultured from various Tp63-expressing tissues e.g, the bladder the oral mucous, the oesophagus or the thymus can acquire new functionality. When exposed to a hair skin microenvironment, these stem cells acquire the capacity to generate hair follicles and sebaceous glands, thus behaving like bona fide hairy skin multipotent stem cells. Genome wide-screen analysis has demonstrated that the stem cells express transcription factors typical of hair follicle differentiation, even though they continue to express some of the genes linked to their origin. This increase in potency demonstrates that lineage restriction is not immutable.

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Functional stem cell aging dictated by skin tissue microenvironment

Project description:Organismal aging in mammals is manifested with architectural alteration and functional decline of multiple organs throughout the body. In aged skin, hairs are sparse, which has led to the hypothesis that the hair follicle stem cells (HFSCs) undergo epidermal differentiation during aging. Here, we employ single cell analysis to interrogate aging-related changes in the HFSCs. Unexpectedly, HFSCs maintain their lineage fidelity and show no signs of shifting to an epidermal fate. Despite maintaining lineage identity, HFSCs do show prevalent transcriptional changes in extracellular matrix genes. Of importance, these HFSC changes are accompanied by profound architectural perturbations in the aging stem cell niche. Upon surveying the dermis from young and aged skin, we also observe age-related changes in many non-epithelial cell types, including resident immune cells, sensory neurons, arrector pili muscles, and blood vessels – all of which have been previously associated with abilities to modulate hair follicle regeneration. Consistent with both intrinsic and extrinsic alterations in stem cell: niche communications, we find that in response to skin wounding, aged HFSCs repair the epidermis, but are defective in hair follicle regeneration. Intriguingly, whereas aged dermis cannot support young HFSCs, aged HFSCs can be rescued when supported by young dermis. Together, these findings favor a model where skin tissue microenvironment plays a dominant role in dictating the molecular properties and activities of HFSCs.

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