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Mechanical Tension Mobilizes Lgr6+ Epidermal Stem Cells to Drive Skin Growth (I)

ABSTRACT: Uniquely among mammalian organs, skin is capable of dramatic size change in adults, yet the mechanisms underlying this striking capacity are unclear. Here, we utilize a system of controlled tissue expansion in mice to uncover cellular and molecular determinants of skin growth. Through machine learning-guided three-dimensional tissue reconstruction, we capture morphometric changes in growing skin. We find that most growth is driven by the proliferation of the epidermis in response to mechanical tension, with more limited changes in dermal and subdermal compartments. Epidermal growth is achieved through preferential activation and differentiation of not Lgr5+, but instead Lgr6+ stem cells of the interfollicular epidermis, driven in part by the Hippo pathway. By single-cell RNA sequencing, we uncover further changes in mechanosensitive and metabolic pathways underlying growth control in the skin. These studies point to therapeutic strategies to enhance skin growth and establish a platform for understanding organ size dynamics in adult mammals.

ORGANISM(S): Mus musculus

PROVIDER: GSE183441 | GEO | 2023/02/03

REPOSITORIES: GEO

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Mechanical Tension Mobilizes Lgr6+ Epidermal Stem Cells to Drive Skin Growth (II)

Project description:Uniquely among mammalian organs, skin is capable of dramatic size change in adults, yet the mechanisms underlying this striking capacity are unclear. Here, we utilize a system of controlled tissue expansion in mice to uncover cellular and molecular determinants of skin growth. Through machine learning-guided three-dimensional tissue reconstruction, we capture morphometric changes in growing skin. We find that most growth is driven by the proliferation of the epidermis in response to mechanical tension, with more limited changes in dermal and subdermal compartments. Epidermal growth is achieved through preferential activation and differentiation of not Lgr5+, but instead Lgr6+ stem cells of the interfollicular epidermis, driven in part by the Hippo pathway. By single-cell RNA sequencing, we uncover further changes in mechanosensitive and metabolic pathways underlying growth control in the skin. These studies point to therapeutic strategies to enhance skin growth and establish a platform for understanding organ size dynamics in adult mammals.

2021-12-30 | GSE186773 | GEO

Mechanical Tension Mobilizes Lgr6+ Epidermal Stem Cells to Drive Skin Growth

Project description:Mechanical Tension Mobilizes Lgr6+ Epidermal Stem Cells to Drive Skin Growth

| PRJNA775997 | ENA

Mechanical Tension Mobilizes Lgr6+ Epidermal Stem Cells to Drive Skin Growth (II)

Project description:Mechanical Tension Mobilizes Lgr6+ Epidermal Stem Cells to Drive Skin Growth (II)

| PRJNA776001 | ENA

Lgr6 Marks Stem Cells in the Hair Follicle that Generate all Cell Lineages of the Skin

Project description:Mammalian epidermis consists of three self-renewing compartments: the hair follicle, sebaceous gland and interfollicular epidermis. We generated knock-in alleles of murine Lgr6, a close relative to the Lgr5 stem cell gene. Lgr6 was expressed in the earliest embryonic hair placodes. In adult hair follicles, Lgr6+ cells resided in a previously uncharacterized region directly above the follicle bulge. They expressed none of the known bulge stem cell markers. Prenatal Lgr6+ cells established the hair follicle, sebaceous gland and interfollicular epidermis. Postnatally, Lgr6+ cells generated sebaceous gland and interfollicular epidermis, while contribution to hair lineages gradually diminished with age. Adult Lgr6+ cells executed long-term wound repair, including the formation of new hair follicles. We conclude that Lgr6 marks the most primitive epidermal stem cell. For the Lgr5 and Lgr6 stem cell comparison RNA was isolated from sorted GFPhi cell fractions of dorsal skin from Lgr5-EGFP-ires-CreERT2 mice and Lgr6-EGFP-ires-CreERT2, respectively (3 mice per group per sort).

2010-03-25 | E-GEOD-20269 | biostudies-arrayexpress

Lgr6 Marks Stem Cells in the Hair Follicle that Generate all Cell Lineages of the Skin

2010-03-26 | GSE20269 | GEO

Transcription profiling of Lgr6+ keratinocyte populations in the epidermis and hair follicle

Project description:RNA sequencing was performed on sorted populations of Lgr6-positive and Lgr6-negative keratinocytes from the interfollicular epidermis and the hair follicle/sebaceous gland, in order to determine the compartment-specific expression signatures of Lgr6+ progenitor cells.

2015-10-22 | E-MTAB-3533 | biostudies-arrayexpress

RNA-Seq of Lgr6 positive and negative cells in mouse mammary gland

Project description:Lgr6-positive cells have been shown to label stem/progenitors cells in several tissues including tongue and skin. However their role in mammary gland has never been investigated. Here we used Lgr6-eGFP-IRES-CreER2 mice to isolate and characterize Lgr6-positive population in mammary gland of 5-week old female mice. Examination of transcriptional differences between Lgr6 positive and negative cells

2016-09-06 | E-GEOD-75648 | biostudies-arrayexpress

RNA-Seq of Lgr6 positive and negative cells in mouse mammary gland

2016-09-06 | GSE75648 | GEO

Mechanical Tension Mobilizes Lgr6+ Epidermal Stem Cells to Drive Skin Growth

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-12-30 | GSE186774 | GEO

LGR6 marks nephron progenitor cells

Project description:Background: Nephron progenitor cells (NPCs) undergo a stepwise process to generate all mature nephron structures. Mesenchymal to epithelial transition (MET) is considered a multi-step process of NPC differentiation to ensure progressive establishment of new nephrons. However, despite this important role, to date, no marker for NPCs undergoing MET in the nephron exists. Results: Here, we identify LGR6 as a NPC marker, expressed in very early cap mesenchyme, pre-tubular aggregates, renal vesicles and in segments of S-shaped bodies, following the trajectory of MET. By using a lineage tracing approach in embryonic explants in combination with confocal imaging and single-cell RNA sequencing, we provide evidence for the multiple fates of LGR6+ cells during embryonic nephrogenesis. Moreover, by using long-term in vivo lineage tracing, we show that postnatal LGR6+ cells are capable of generating the multiple lineages of the nephrons. Conclusion: Given the profound early mesenchymal expression and MET signature of LGR6+ cells, together with the lineage tracing of mesenchymal LGR6+ cells, we conclude that LGR6+ cells contribute to all nephrogenic segments by undergoing MET. LGR6+ cells can therefore be considered an early committed NPC population during embryonic and postnatal nephrogenesis with potential regenerative capability.

2021-05-25 | GSE164795 | GEO

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