In Vivo Cell Fate Tracing Provides No Evidence for Mesenchymal to Epithelial Transition in Adult Fallopian Tube and Uterus

Ghosh, Arnab; Syed, Shafiq M.; Kumar, Manish; Carpenter, Tyler J.; Teixeira, Jose; Houairia, Nathaniel; Negi, Sumedha; Tanwar, Pradeep S.

doi:10.1016/j.celrep.2020.107631

Cited by 34 publications

(40 citation statements)

References 51 publications

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“…However, a recent cell fate tracing study found that the conclusive evidence for the conversion of mesenchymal cells to epithelial cells in adult uterine is lacking. The study of the embryonal cell lineage tracing with reporters driven by mesenchymal cell marker genes of the female reproductive tract (AMHR2, CSPG4, and PDGFRβ) showed that these reporters are also expressed in some oviductal and uterine epithelial cells at birth [ 110 ].…”

Section: Endometrial Epithelial Stem/progenitor Cellsmentioning

confidence: 99%

Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis

et al. 2021

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Endometrial stem/progenitor cells have been proved to exist in periodically regenerated female endometrium and can be divided into three categories: endometrial epithelial stem/progenitor cells, CD140b+CD146+ or SUSD2+ endometrial mesenchymal stem cells (eMSCs), and side population cells (SPs). Endometrial stem/progenitor cells in the menstruation blood are defined as menstrual stem cells (MenSCs). Due to their abundant sources, excellent proliferation, and autotransplantation capabilities, MenSCs are ideal candidates for cell-based therapy in regenerative medicine, inflammation, and immune-related diseases. Endometrial stem/progenitor cells also participate in the occurrence and development of endometriosis by entering the pelvic cavity from retrograde menstruation and becoming overreactive under certain conditions to form new glands and stroma through clonal expansion. Additionally, the limited bone marrow mesenchymal stem cells (BMDSCs) in blood circulation can be recruited and infiltrated into the lesion sites, leading to the establishment of deep invasive endometriosis. On the other hand, cell derived from endometriosis may also enter the blood circulation to form circulating endometrial cells (CECs) with stem cell-like properties, and to migrate and implant into distant tissues. In this manuscript, by reviewing the available literature, we outlined the characteristics of endometrial stem/progenitor cells and summarized their roles in immunoregulation, regenerative medicine, and endometriosis, through which to provide some novel therapeutic strategies for reproductive and cancerous diseases.

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Section: Endometrial Epithelial Stem/progenitor Cellsmentioning

confidence: 99%

Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis

et al. 2021

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“…A comprehensive investigation into a role for MET in endometrial regeneration using a number of different lineage tracing mouse lines indicates that mesenchymal reporter-positive epithelial cells were identified at birth and maintained in adult epithelium, as expected for a mesodermal-derived epithelium. However, evidence of MET of adult mesenchymal cells, particularly during postpartum repair, was not identified suggesting that it is unlikely that the mesenchyme contributes to the adult epithelium (Ghosh et al, 2020).…”

Section: Role Of Endometrial Epithelial Stem/progenitor Cells In Re-epithelization and Post-partum Regenerationmentioning

confidence: 99%

The Elusive Endometrial Epithelial Stem/Progenitor Cells

Cousins

Pandoy

Jin

et al. 2021

Front. Cell Dev. Biol.

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The human endometrium undergoes approximately 450 cycles of proliferation, differentiation, shedding and regeneration over a woman’s reproductive lifetime. The regenerative capacity of the endometrium is attributed to stem/progenitor cells residing in the basalis layer of the tissue. Mesenchymal stem cells have been extensively studied in the endometrium, whereas endometrial epithelial stem/progenitor cells have remained more elusive. This review details the discovery of human and mouse endometrial epithelial stem/progenitor cells. It highlights recent significant developments identifying putative markers of these epithelial stem/progenitor cells that reveal their in vivo identity, location in both human and mouse endometrium, raising common but also different viewpoints. The review also outlines the techniques used to identify epithelial stem/progenitor cells, specifically in vitro functional assays and in vivo lineage tracing. We will also discuss their known interactions and hierarchy and known roles in endometrial dynamics across the menstrual or estrous cycle including re-epithelialization at menses and regeneration of the tissue during the proliferative phase. We also detail their potential role in endometrial proliferative disorders such as endometriosis.

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“…Specific features of ECM composition and organization by SCs regulate their functional state through feedback mediated by integrin signaling and form a unique topography of connective tissue and determine its interaction with other cell types ( Mouw et al, 2014 ). Thus, properties of matrix produced by EndoSC can affect not only fibrogenesis but also angiogenesis and epithelialization, which are important for endometrial healing and provide an intriguing task for investigation of mechanisms in this field ( Fan et al, 2008 ; Owusu-Akyaw et al, 2019 ; Yin et al, 2019 ; Ghosh et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Scar-Free Healing of Endometrium: Tissue-Specific Program of Stromal Cells and Its Induction by Soluble Factors Produced After Damage

Eremichev

Kulebyakina

Alexandrushkina

et al. 2021

Front. Cell Dev. Biol.

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Besides certain exceptions, healing of most tissues in the human body occurs via formation of scar tissue, rather than restoration of lost structures. After extensive acute injuries, this phenomenon substantially limits the possibility of lost function recovery and, in case of chronic injury, it leads to pathological remodeling of organs affected. Managing outcomes of damaged tissue repair is one of the main objectives of regenerative medicine. The first priority for reaching it is comparative investigation of mechanisms responsible for complete restoration of damaged tissues and mechanisms of scarring. However, human body tissues that undergo complete scar-free healing are scarce. The endometrium is a unique mucous membrane in the human body that heals without scarring after various injuries, as well as during each menstrual cycle (i.e., up to 400 times during a woman’s life). We hypothesized that absence of scarring during endometrial healing may be associated with tissue-specific features of its stromal cells (SCs) or their microenvironment, since SCs transform into myofibroblasts—the main effector link of scarring. We found that during healing of the endometrium, soluble factors are formed that inhibit the transition of SCs into myofibroblasts. Without influence of these factors, the SCs of the endometrium undergo transformation into myofibroblasts after transforming growth factor β1 (TGF-β1) treatment as well as the SCs from tissues that heal by scarring—skin or fat. However, unlike the latter, endometrial SCs organize extracellular matrix (ECM) in a specific way and are not prone to formation of bulky connective tissue structures. Thus, we may suggest that tissue-specific features of endometrial SCs along with effects of soluble factors secreted in utero during menstruation ensure scar-free healing of human endometrium.

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In Vivo Cell Fate Tracing Provides No Evidence for Mesenchymal to Epithelial Transition in Adult Fallopian Tube and Uterus

Cited by 34 publications

References 51 publications

Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis

Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis

The Elusive Endometrial Epithelial Stem/Progenitor Cells

Scar-Free Healing of Endometrium: Tissue-Specific Program of Stromal Cells and Its Induction by Soluble Factors Produced After Damage

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