Skip to main content
Premium Trial:

Request an Annual Quote

Wound Healing Dynamics Traced With Single-Cell Transcriptomics

NEW YORK (GenomeWeb) – A single-cell transcriptome analysis has spelled out the activity of skin stem cells as they respond to skin injuries and participate in the processes that heal these wounds.

"[O]ur results reveal the importance of rapid transcriptional adaptations during wound repair in order to gain the ability to react to injury by interacting with the wound environment," corresponding author Maria Kasper, a biosciences, nutrition, and innovative medicine researcher at the Karolinska Institute, and her colleagues wrote.

She and her Karolinska Institute colleagues used lineage tracing and single-cell RNA sequencing to track hair follicle bulge and interfollicular epidermis (IFE) stem cells expressing Lgr5 and Lgr6 receptor proteins, respectively, during wound healing. In the hair follicle bulge cells, for example, they saw a shift toward transcriptional features resembling those found in the IFE cells, coupled with receptor remodeling in the Lgr5-positive cell lineage to boost interactions with other wound healing players.

"When contributing to re-epithelialization, Lgr5 progeny gradually replaced their bulge identity with an IFE identity," the authors reported, "and this process started already before Lgr5 left the bulge."

In contrast, the team noted that cells stemming from the Lgr6-positive lineage appeared to inherently possess the potential for such interactions, though the early and late stages of wound healing still prompted specific transcriptional signatures. The findings appeared online today in Cell Reports.

In the past, the authors argued, the "understanding of the transcriptional adaptations of individual [stem cells] and their progeny has been hampered by the inability to obtain transcriptional profiles of individual cells, combined with a method to distinguish progeny of different epidermal [stem cell] populations in the wound."

With that in mind, the researchers used the so-called Tomato lineage tracing system to follow Lgr5-positive and Lgr6-positive hair follicle and IFE cells in mice with small dorsal punch wounds. They used an Illumina HiSeq instrument to do single-cell RNA sequencing on 1,873 individual cells from cells surrounding the injury over the first 10 days of healing and in fully healed tissue.

With these data, the team described gene expression dynamics in the hair follicle bulge and IFE stem cells, uncovering altered cell states and corresponding molecular interactions after wound healing, while defining a shared IFE cell-related transcriptome signature associated with wound healing.

Together, the work "reveals how different [stem cells] respond and adapt to a new environment, potentially explaining cellular plasticity of many epithelial tissues," the authors wrote.

More broadly, they suggested, the study approach "demonstrates that the combination of lineage tracing with single-cell transcriptomics represents a powerful strategy to resolve transcriptional programs occurring in independent cells of distinct origins during tissue repair processes."