HOX genes in stem cells: Maintaining cellular identity and regulation of differentiation

Steens, Jennifer; Klein, Diana

doi:10.3389/fcell.2022.1002909

Cited by 22 publications

(10 citation statements)

References 202 publications

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“…The observation that single HOX transcription factors could be found within the most differentially expressed genes in MSCs compared to FIB ( Figures 1A, B ), together with the already established HOX code as an integral regulator of (stem) cell identity and cell fate for MSCs particularly for VW-MSCs ( 16 , 21 , 27 , 44 ), encouraged us to designate a HOX-specific-expression pattern and thus establishing a HOX code for fibroblasts ( Figure 4 ). Herein, transcript levels of the HOX candidates as detected by the microarray analysis (23 HOX genes) revealed obvious differences between both mesodermal cell types ( Figures 4A, B ).…”

Section: Resultsmentioning

confidence: 99%

Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts

Budeus,

Unger,

Hess

et al. 2023

Front. Immunol.

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IntroductionMesenchymal stem cells (MSCs) are considered to be the most promising stem cell type for cell-based therapies in regenerative medicine. Based on their potential to home to diseased body sites following a therapeutically application, these cells could (i) differentiate then into organ-specific cell types to locally restore injured cells or, most prominently, (ii) foster tissue regeneration including immune modulations more indirectly by secretion of protective growth factors and cytokines. As tissue-resident stem cells of mesenchymal origin, these cells are morphologically and even molecularly- at least concerning the classical marker genes- indistinguishable from similar lineage cells, particularly fibroblasts.MethodsHere we used microarray-based gene expression and global DNA methylation analyses as well as accompanying computational tools in order to specify differences between MSCs and fibroblasts, to further unravel potential identity genes and to highlight MSC signaling pathways with regard to their trophic and immunosuppressive action.ResultsWe identified 1352 differentially expressed genes, of which in the MSCs there is a strong signature for e.g., KRAS signaling, known to play essential role in stemness maintenance, regulation of coagulation and complement being decisive for resolving inflammatory processes, as well as of wound healing particularly important for their regenerative capacity. Genes upregulated in fibroblasts addressed predominately transcription and biosynthetic processes and mapped morphological features of the tissue. Concerning the cellular identity, we specified the already known HOX code for MSCs, established a potential HOX code for fibroblasts, and linked certain HOX genes to functional cell-type-specific properties. Accompanied methylation profiles revealed numerous regions, especially in HOX genes, being differentially methylated, which might provide additional biomarker potential.DiscussionConclusively, transcriptomic together with epigenetic signatures can be successfully be used for the definition (cellular identity) of MSCs versus fibroblasts as well as for the determination of the superior functional properties of MSCs, such as their immunomodulatory potential.

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Section: Resultsmentioning

confidence: 99%

Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts

Budeus,

Unger,

Hess

et al. 2023

Front. Immunol.

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“…The homeobox genes are originally cloned based on the function in the normal development 41 . They have also been reported to participate in the pathogenesis of many diseases 42,43 .…”

Section: Discussionmentioning

confidence: 99%

“…The homeobox genes are originally cloned based on the function in the normal development. 41 They have also been reported to participate in the pathogenesis of many diseases. 42,43 Hence, the homeobox genes many have the potential to orchestrate the transcription network.…”

Section: En2 Serves As a Master Regulator Of The Se In The Tnc Locusmentioning

confidence: 99%

Engrailed 2 serves as a master regulator of the super‐enhancer in the TNC gene locus in non‐small cell lung cancer

Li,

Jiang,

Wang

et al. 2023

Environmental Toxicology

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Engrailed 2 (EN2) is a homeodomain‐containing protein that is dysregulated in many types of cancer. However, the role of EN2 in non‐small cell lung cancer (NSCLC) and the mechanism underlying its biological function are largely unclear. Here, we showed that EN2 played an oncogenic function in NSCLC and greatly enhanced the malignant phenotype of NSCLC cells. Meanwhile, EN2 was able to boost the expression of a well‐studied oncogenic Tenascin‐C (TNC) gene, which in turn activated the AKT signaling pathway. Interestingly, we found that EN2 directly bound to the super‐enhancer (SE) region in the TNC locus. The histone marker H3K27ac was also enriched in the region, indicating the activation of the SE. Treatment of the cells with JQ1, an inhibitor of SE activity, abrogated the effect of EN2 on the expression of TNC and phosphorylation of AKT‐Ser473. Collectively, our work unveils a novel mode of EN2 function, in which EN2 governs the SE in the TNC locus, consequently activating the oncogenic TNC–AKT axis in NSCLC.

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“…The purpose of bone marrow transplantation (BMT) is to transplant hematopoietic stem cells (46,47). Stem cells have the ability to replicate and differentiate into hematopoietic and immune active cells (48). BMT is associated with HLA and it is therefore a requirement that the HLA-A, B, DR and DQ isotypes of the donor and recipient are as compatible as possible (49).…”

Section: Physiological Function and Structure Of Hlamentioning

confidence: 99%

Human leukocyte antigen and tumor immunotherapy (Review)

Liu

Mou²,

et al. 2023

Int J Oncol

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Malignant tumors seriously endanger human health and life, and restrict economic development. Human leukocyte antigen (HLA) is the expression product of the human major histocompatibility complex, which, at present, is the most complex known polymorphic system. The polymorphism and expression of HLA molecules have been demonstrated to be associated with the occurrence and development of tumors. HLA molecules can regulate the proliferation of tumor cells and inhibit antitumor immunity. In the present review, the structure and function of HLA molecules, the polymorphism and expression of HLA in tumor tissue, the roles of HLA in tumor cells and tumor immunity, and the potential clinical application of HLA in tumor immunotherapy are summarized. The overall aim of the present review is to provide relevant information for the development of antitumor immunotherapies involving HLA in the clinic. Contents 1. Introduction 2. Physiological function and structure of HLA 3. HLA polymorphism and cancer 4. Function of HLA in tumor immunity 5. Clinical significance of HLA in tumor immunotherapy 6. Future perspectives

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HOX genes in stem cells: Maintaining cellular identity and regulation of differentiation

Cited by 22 publications

References 202 publications

Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts

Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts

Engrailed 2 serves as a master regulator of the super‐enhancer in the TNC gene locus in non‐small cell lung cancer

Human leukocyte antigen and tumor immunotherapy (Review)

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