Role of HNRNPL in human epidermal stem and progenitor cells
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ABSTRACT:
PROVIDER: PRJNA682191 | ENA |
REPOSITORIES: ENA
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Project description:HNRNPL plays a critical role in regulating epidermal stem and progenitor cell function through regulating integrin gene expression at transcriptional level.
2021-09-21 | GSE162546 | GEO
Project description:Millions suffer from skin diseases. Functional epidermal stem cells are needed in skin therapy or drug screening in vitro. We obtained functional epidermal stem cells with intact stemness and cell junctions by treating them with wnt3a. Moreover, epidermal stem cell-derived exosomes were useful in epidermal development. Finally, functional epidermal 3D organoids with polarity were cultured using wnt3a and the supernatant derived from epidermal stem cells and fresh medium in a 1:1 ratio. These results provide novel directions for the improvement of skin organoids and their potential in clinical application.
2020-07-14 | PXD020351 | iProX
Project description:The regulatory circuits that coordinate epidermal differentiation during development are still not fully understood. Here we report that the transcriptional regulator ID1 is enriched in basal epidermal progenitor cells and find ID1 expression to be diminished upon differentiation. In utero silencing of Id1 impairs progenitor cell proliferation, leads to precocious delamination of targeted progenitor cells and enables differentiated keratinocytes to retain progenitor markers and characteristics. Transcriptional profiling suggests ID1 acts by mediating adhesion to the basement membrane while inhibiting spinous layer differentiation. Co-immunoprecipitation reveals ID1 binding to transcriptional regulators of the class I bHLH family. We localize bHLH Tcf3, Tcf4 and Tcf12 to epidermal progenitor cells during epidermal stratification and established TCF3 as a downstream effector of ID1-mediated epidermal proliferation. Finally, we identify crosstalk between CEBPA, a known mediator of epidermal differentiation, and Id1 and demonstrate that CEBPA antagonizes BMP-induced activation of Id1. Our work establishes ID1 as a key coordinator of epidermal development, acting to balance progenitor proliferation with differentiation and unveils how functional crosstalk between CEBPA and Id1 orchestrates epidermal lineage progression.
2022-10-14 | GSE215055 | GEO
Project description:We used microarrays to assess the global gene expression profiles of cancer stem cells which were isolated from cutaneous squamous cell carcinomas which developed when WT, TGF beta receptor II ko, FAK KO, and TGF beta receptor II/FAK double KO were subjected to continuous DMBA treatment. Squamous cell carcinoma stem cells were compared to epidermal progenitor cells (CD49fhighCD34low) and hair follicle bulge stem cells (CD49fhighCD34high).
2011-12-30 | GSE29328 | GEO
Project description:The multifunctional RNA-binding protein hnRNPL has been implicated in antibody class switching but its broader function in B cells is unknown. Here, we show that hnRNPL is essential for B cell activation, and thereby germinal center and antibody responses. Upon activation, hnRNPL-deficient B cells show proliferation defects and increased apoptosis. The comparative analysis of RNA-seq data from B cells and another 8 hnRNPL-depleted cell types reveals a common function in the Myc and E2F transcriptional programs required for proliferation, likely borne out of a large alternative splicing change affecting multiple transcription regulators. Notably, while individual gene expression changes were cell type specific, several alternative splicing events affecting histone modifiers like SIRT1, KDM6A, and NSD2, were conserved across cell types, which could contribute to gene expression changes upon hnRNPL loss. SIRT1 reduction due to alternative splicing, and other transcriptional changes suggested mitochondrial defects in hnRNPL-deficient B cells. We confirmed dysfunctional mitochondria and ROS overproduction, which could explain the B cell activation defect. Thus, hnRNPL is essential for the resting to activated B cell transition by regulating transcriptional programs, most likely by splicing regulation affecting several histone modifiers.
2024-04-24 | GSE242069 | GEO
Project description:Transcriptomic profile of Fanconi anemia (FA) epidermal stem and progenitor cells (ESPCs)
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Project description:In the current project with aim to unequivocally characterize a novel splicing-regulatory network that proves to be a central mediator of endothelial barrier function and vascular integrity. At the core of this network is the endothelial enriched lncRNA NTRAS (annotated as RP11-354k1.1) is shown to control alternative splicing decisions in HUVECs through interplaying with splicing factor hnRNPL. Specifically, in the project we show that NTRAS sequesters the splicing factor hnRNPL through a CA dinucleotide motif, to enhance TJP1 exon 20 usage, thereby TJP1α+ isoform. In turn disrupting TJP1α+ isoform expression impaired endothelial barrier function. Collectively, this splicing-regulatory network might prove fundamental in unlocking new interventions strategic to prevent or reverse vascular leakage.
2022-01-10 | E-MTAB-11311 | biostudies-arrayexpress
Project description:We used microarrays to assess the global gene expression profiles of cancer stem cells which were isolated from cutaneous squamous cell carcinomas which developed when WT, TGF beta receptor II ko, FAK KO, and TGF beta receptor II/FAK double KO were subjected to continuous DMBA treatment. Squamous cell carcinoma stem cells were compared to epidermal progenitor cells (CD49fhighCD34low) and hair follicle bulge stem cells (CD49fhighCD34high). Squamous cell carcinoma was initiated by continuous DMBA treatment (complete carcinogenesis). Cancer cells were sorted based on high CD29 and CD49f expression, infected with a retrovirus expressing a triple modality reporter (luciferase, RFP, thymidine kinase) and grafted onto nude recipient mice. RFP positive lineage was separated into CD29 high, CD49f high and CD34 low; or CD29high, CD49f high and CD34high squamous cell carcinoma initiating cells.
2011-12-30 | E-GEOD-29328 | biostudies-arrayexpress
Project description:PRMT1 and CSNK1a1 control epidermal progenitor maintenance
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Project description:Maintenance of high-turnover tissues such as the epidermis requires a tight balance between stem and progenitor cell proliferation and differentiation. The molecular mechanisms governing this process are an area of active investigation. Here we show that HNRNPK, a multifunctional protein, is necessary to prevent premature differentiation and sustains the proliferative capacity of epidermal stem and progenitor cells. To prevent premature differentiation of progenitor cells, HNRNPK recruits DDX6 to a subset of mRNAs that code for transcription factors that induce differentiation. Upon binding, these mRNAs such as GRHL3, KLF4, and ZNF750 are degraded which prevents premature differentiation. To sustain the proliferative capacity of the epidermis, HNRNPK recruits RNA polymerase II to genomic sites of proliferation genes such as MYC, FGFBP1, PTHLH, ITGB4 to promote their expressions. Our study establishes a prominent role for HNRNPK in maintaining adult tissue homeostasis through both transcriptional and post-transcriptional mechanisms.
2019-07-23 | GSE122327 | GEO