ArticleDevelopment (Cambridge, England)2011
Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury.
Article in Development (Cambridge, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 126 citations in OpenAlex.
- MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2.Journal of experimental & clinical cancer research : CR · 2019Trial
- Interplay of ELF5, GATA-3 and FLI-1 regulate malignant transformation of keratinocytes.Scientific reports · 2026Article
- Article
- An updated guide to hair follicle stem cell markers and changes in their expression with aging.JID innovations : skin science from molecules to population health · 2026Review
- Review
- A multi-omic single-cell landscape of perinatal mouse skin maps lineage specification and reveals shared dynamics in human fetal skin.Experimental & molecular medicine · 2026Article
- Cerium-doped prussian blue nanozymes for bone regeneration and osteoprotection by Lhx2 in sutural distraction osteogenesis through multi-omics analysis.Journal of nanobiotechnology · 2026Article
- Transcriptional and epigenetic mechanisms governing epidermal stem cell regulation.Frontiers in cell and developmental biology · 2026Review
- LHX2: a transcription factor in development, homeostasis, repair, and disease.Frontiers in cell and developmental biology · 2026Review
- Integrated Single-cell Analysis Uncovers Regulatory Logic of Cranial Ectoderm Development.bioRxiv : the preprint server for biology · 2025Article
- PIEZO1-mediated calcium signaling reinforces mechanical properties of hair follicle stem cells to promote quiescence.Science advances · 2025Article
- Asxl1 regulates optic cup development through interaction with Lhx2 and epigenetic modulation of Wnt signaling.Animal cells and systems · 2025Article
- TMT-based quantitative proteomics reveals the genetic mechanisms of secondary hair follicle development in fine-wool sheep.PloS one · 2025Article
- Curcumin-primed milk-derived extracellular vesicles remodel hair follicle microenvironment for the treatment of androgenetic alopecia.Regenerative biomaterials · 2025Article
- Article
- Recent progress in hair follicle stem cell markers and their regulatory roles.World journal of stem cells · 2024Review
- The Biology and Genomics of Human Hair Follicles: A Focus on Androgenetic Alopecia.International journal of molecular sciences · 2024Review
- Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages.Science advances · 2024Article
- Biological and mechanical influence of three-dimensional microenvironment formed in microwell on multicellular spheroids composed of heterogeneous hair follicle stem cells.Scientific reports · 2023Article
- Insights into Repeated Renal Injury Using RNA-Seq with Two New RPTEC Cell Lines.International journal of molecular sciences · 2023Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
The Lhx2 transcription factor plays essential roles in morphogenesis and patterning of ectodermal derivatives as well as in controlling stem cell activity. Here, we show that during murine skin morphogenesis, Lhx2 is expressed in the hair follicle (HF) buds, whereas in postnatal telogen HFs Lhx2(+) cells reside in the stem cell-enriched epithelial compartments (bulge, secondary hair germ) and co-express selected stem cell markers (Sox9, Tcf4 and Lgr5). Remarkably, Lhx2(+) cells represent the vast majority of cells in the bulge and secondary hair germ that proliferate in response to skin injury. This is functionally important, as wound re-epithelization is significantly retarded in heterozygous Lhx2 knockout (+/-) mice, whereas anagen onset in the HFs located closely to the wound is accelerated compared with wild-type mice. Cell proliferation in the bulge and the number of Sox9(+) and Tcf4(+) cells in the HFs closely adjacent to the wound in Lhx2(+/-) mice are decreased in comparison with wild-type controls, whereas expression of Lgr5 and cell proliferation in the secondary hair germ are increased. Furthermore, acceleration of wound-induced anagen development in Lhx2(+/-) mice is inhibited by administration of Lgr5 siRNA. Finally, Chip-on-chip/ChIP-qPCR and reporter assay analyses identified Sox9, Tcf4 and Lgr5 as direct Lhx2 targets in keratinocytes. These data strongly suggest that Lhx2 positively regulates Sox9 and Tcf4 in the bulge cells, and promotes wound re-epithelization, whereas it simultaneously negatively regulates Lgr5 in the secondary hair germ and inhibits HF cycling. Thus, Lhx2 operates as an important regulator of epithelial stem cell activity in the skin response to injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.