Isolation and Characterization of Progenitor Cells in Uninjured, Adult Rat Lacrimal Gland

Shatos, Marie A.; Haugaard‐Kedström, Linda M.; Hodges, Robin R.; Dartt, Darlene A.

doi:10.1167/iovs.11-9025

Cited by 52 publications

(66 citation statements)

References 32 publications

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“…Pax6 regulates LG cell proliferation and branching morphogenesis and has a major role in maintenance of the adult ocular tissues. 59,60 Klf4 is the most abundant gene in ocular tissues, including the LG, and has important roles in cell proliferation and differentiation. Sox9 expression is restricted to the LG epithelium.…”

Section: Stem Cell/progenitor Cell Expression Signatures Are Altered mentioning

confidence: 99%

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Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

Umazume

Thomas

Campbell

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The adult lacrimal gland (LG) is highly regenerative and is able to repair itself even after substantial damage; however, this ability to regenerate is lost with the development of dry eye conditions in chronically inflamed LGs.This study compares changes in the cell adhesion and cell matrix molecules and stem cell transcription factors in the LGs of healthy mice and of two mouse models of Sjögren's syndrome: nonobese diabetic (NOD) and MRLlpr/lpr (MRL/lpr) mice during the early stage of inflammation. METHODS. TheLGs from 12-to 13-week-old female MRL/lpr and male NOD mice along with their respective control strains were harvested and divided into three pieces and processed for quantitative (q) RT-PCR and qRT-PCR Arrays, histology, immunohistochemistry, and Western blotting. RESULTS. The extracellular matrix (ECM) and adhesion molecules RT2 -PCR array combined with protein expression data revealed changes in the expression of integrins, matrix metalloproteinases, and other molecules, which are associated largely with invasion, attachment, and expansion of the lymphocytic cells, whereas changes in the stem cell transcription factors revealed substantial decrease in expression of transcription factors associated with epithelial stem/progenitor cell lineage. CONCLUSIONS.We concluded that the expression of several important ECM components is significantly deregulated in the LG of two murine models of Sjögren's syndrome, suggesting an alteration of the epithelial stem/progenitor cell niche. This may result in profound effects on localization, activation, proliferation, and differentiation of the LG stem/progenitor cells and, therefore, LG regeneration.

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Section: Stem Cell/progenitor Cell Expression Signatures Are Altered mentioning

confidence: 99%

“…Pax6 is one of the most important regulators of LG development and regeneration. 29,58,60,64,65 Oct4 is an important pluripotency factor that regulates self-renewal of many cell types. [66][67][68][69] We found a substantial decrease in number of Pax6 expressing cells in MRL/lpr (Figs.…”

Section: Stem Cell/progenitor Cell Expression Signatures Are Altered mentioning

confidence: 99%

Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

Umazume

Thomas

Campbell

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…Myoepithelial cells surround the acinar cells on the basal side and because they contain α-smooth muscle actin (αSMA), it is believed that they contract to help expel the secretory products, as in the salivary and mammary glands (Ohtomo et al, 2011). More recently we demonstrated that a population of myoepithelial cells could serve as stem/progenitor cells for the LG (Shatos et al, 2012a). …”

Section: Introductionmentioning

confidence: 99%

“…A third possibility is the myoepithelial cell. In rat LG and injured mouse LG, myoepithelial cells are positive for stem/progenitor cell markers (Shatos et al, 2012a; You et al, 2012). No published evidence has eliminated any of these cell types, mesenchymal, epithelial, or myoepithelial, from being stem/progenitor cells in the LG.…”

Section: Introductionmentioning

confidence: 99%

Alteration in cellular turnover and progenitor cell population in lacrimal glands from thrombospondin 1 −/− mice, a model of dry eye

Shatos

Hodges

Morinaga

et al. 2016

Experimental Eye Research

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The purpose of this study was to investigate the changes that occur in the lacrimal glands (LGs) in female thrombospondin 1 knockout (TSP1−/−) mice, a mouse model of the autoimmune disease Sjogren’s syndrome. The LGs of 4, 12, and 24 week-old female TSP1−/− and C57BL/6J (wild type, WT) mice were used. qPCR was performed to measure cytokine expression. To study the architecture, LG sections were stained with hematoxylin and eosin. Cell proliferation was measured using bromo-deoxyuridine and immunohistochemistry. Amount of CD47 and stem cell markers was analyzed by western blot analysis and location by immunofluorescence microscopy. Expression of stem cell transcription factors was performed using Mouse Stem Cell Transcription Factors RT2 Profiler PCR Array. Cytokine levels significantly increased in LGs of 24 week-old TSP1−/− mice while morphological changes were detected at 12 weeks. Proliferation was decreased in 12 week-old TSP1−/− mice. Three transcription factors were overexpressed and eleven underexpressed in TSP1−/− compared to WT LGs. The amount of CD47, Musashi1, and Sox2 was decreased while the amount of ABCG2 was increased in 12 week-old TSP1−/− mice. We conclude that TSP1 is necessary for maintaining normal LG homeostasis. Absence of TSP1 alters cytokine levels and stem cell transcription factors, LG cellular architecture, decreases cell proliferation, and alters amount of stem cell markers.

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“…On the other hand, an immature stem-like population expressing the putative stem cell markers nestin, Mushahi1 and ABCG2 has been identified in the myoepithelium from the uninjured rat lacrimal gland. These cells can be expanded in culture and differentiated into multiple lineages, suggesting a myoepithelial origin for the intrinsic progenitor cells (Shatos et al, 2012). Single cells isolated from lacrimal gland epithelial cell cultures have also been shown to possess sphere-forming capabilities characteristic of stem cells, but these cells did not express the myoepithelial marker α-SMA (Kobayashi et al, 2012).…”

Section: The Molecular Mechanism Of Lacrimal Gland Developmentmentioning

confidence: 99%

Lacrimal gland development: From signaling interactions to regenerative medicine

Garg

Zhang

2017

Developmental Dynamics

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The lacrimal gland plays a pivotal role in keeping the ocular surface lubricated, and protecting it from environmental exposure and insult. Dysfunction of the lacrimal gland results in deficiency of the aqueous component of the tear film, which can cause dryness of the ocular surface, also known as the aqueous-deficient dry eye disease. Left untreated, this disease can lead to significant morbidity, including frequent eye infections, corneal ulcerations and vision loss. Current therapies do not treat the underlying deficiency of the lacrimal gland, but merely provide symptomatic relief. To develop more sustainable and physiological therapies, such as in vivo lacrimal gland regeneration or bioengineered lacrimal gland implants, a thorough understanding of lacrimal gland development at the molecular level is of paramount importance. Based on the structural and functional similarities between rodent and human eye development, extensive studies have been undertaken to investigate the signaling and transcriptional mechanisms of lacrimal gland development using mouse as a model system. In this review, we describe the current understanding of the extrinsic signaling interactions and the intrinsic transcriptional network governing lacrimal gland morphogenesis, as well as recent advances in the field of regenerative medicine aimed at treating dry eye disease.

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Isolation and Characterization of Progenitor Cells in Uninjured, Adult Rat Lacrimal Gland

Cited by 52 publications

References 32 publications

Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

Alteration in cellular turnover and progenitor cell population in lacrimal glands from thrombospondin 1 −/− mice, a model of dry eye

Lacrimal gland development: From signaling interactions to regenerative medicine

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