Transcription Factor PAX6 (Paired Box 6) Controls Limbal Stem Cell Lineage in Development and Disease

Li, Gen; Xu, Fan; Zhu, Jie; Krawczyk, Michał; Zhang, Ying; Yuan, Jing; Patel, Sherrinal; Wang, Yujuan; Lin, Ying; Zhang, Ming; Cai, Huimin; Chen, Daniel; Zhang, Meixia; Cao, Guiqun; Yeh, Erika; Lin, Danni; Qiao, Shan; Li, Wenwen; Sen, George L.; Afshari, Natalie A.; Chen, Shaochen; Maas, Richard L.; Fu, Xiang‐Dong; Zhang, Kang; Liu, Yizhi; Ouyang, Hong

doi:10.1074/jbc.m115.662940

Cited by 59 publications

(48 citation statements)

References 29 publications

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“…PAX6, a protein initially found to regulate neural stem cell self-renewal and differentiation, marks progenitor cells in the developing lens, cornea and lacrimal glands (Li et al , 2015; Lin et al , 2016). PAX6 is essential for ocular organ formation as shown by the absence of eyes and lacrimal gland in Pax6−/− embryos (Hill et al , 1991) and impaired eye and lacrimal gland morphogenesis in embryos heterozygous for Pax6 (Makarenkova et al , 2000; Remez et al , 2017).…”

Section: Salivary Gland Developmentmentioning

confidence: 99%

Salivary gland stem cells: A review of development, regeneration and cancer

Emmerson

Knox

2018

Genesis

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Salivary glands are responsible for maintaining the health of the oral cavity and are routinely damaged by therapeutic radiation for head and neck cancer as well as by autoimmune diseases such as Sjögren's syndrome. Regenerative approaches based on the reactivation of endogenous stem cells or the transplant of exogenous stem cells hold substantial promise in restoring the structure and function of these organs to improve patient quality of life. However, these approaches have been hampered by a lack of knowledge on the identity of salivary stem cell populations and their regulators. In this review we discuss our current knowledge on salivary stem cells and their regulators during organ development, homeostasis and regeneration. As increasing evidence in other systems suggests that progenitor cells may be a source of cancer, we also review whether these same salivary stem cells may also be cancer initiating cells.

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Section: Salivary Gland Developmentmentioning

confidence: 99%

Salivary gland stem cells: A review of development, regeneration and cancer

Emmerson

Knox

2018

Genesis

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“…An early eye field transcription factor, PAX6, can be first detected in the surface ectoderm of the developing mouse at embryonic (E) eight stage, and is subsequently expressed in the developing corneal epithelium at E12.5 . Recent genetic lineage tracing studies in Pax6/Cre (P0–3.9‐GFPCre) mice crossed to ROSA mT/mG reporter mice showed greed fluorescent protein (GFP) expression in the entire corneal epithelium suggesting that Pax6‐expressing progenitors contribute to corneal epithelial generation and regeneration during development and adulthood, which raised the possibility that Pax6+ cells within the surface ectoderm represent the cells of origin of LSC. This possibility is also supported by findings in Pax6+/− mice that revealed that Pax6 haploinsufficiency results in reduced expression of the corneal epithelial differentiation marker Krt12 and increased corneal vascularization consistent with a LSCD phenotype …”

Section: Developmental Origin Of Lsc and Their Nichementioning

confidence: 99%

Limbal stem cells: identity, developmental origin, and therapeutic potential

González

Sasamoto

Ksander

et al. 2017

WIREs Developmental Biology

103

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The cornea is our window to the world and our vision is critically dependent on corneal clarity and integrity. Its epithelium represents one of the most rapidly regenerating mammalian tissues, undergoing full-turnover over the course of approximately 1-2 weeks. This robust and efficient regenerative capacity is dependent on the function of stem cells residing in the limbus, a structure marking the border between the cornea and the conjunctiva. Limbal stem cells (LSC) represent a quiescent cell population with proliferative capacity residing in the basal epithelial layer of the limbus within a cellular niche. In addition to LSC, this niche consists of various cell populations such as limbal stromal fibroblasts, melanocytes and immune cells as well as a basement membrane, all of which are essential for LSC maintenance and LSC-driven regeneration. The LSC niche's components are of diverse developmental origin, a fact that had, until recently, prevented precise identification of molecularly defined LSC. The recent success in prospective LSC isolation based on ABCB5 expression and the capacity of this LSC population for long-term corneal restoration following transplantation in preclinical in vivo models of LSC deficiency underline the considerable potential of pure LSC formulations for clinical therapy. Additional studies, including genetic lineage tracing of the developmental origin of LSC will further improve our understanding of this critical cell population and its niche, with important implications for regenerative medicine. WIREs Dev Biol 2018, 7:e303. doi: 10.1002/wdev.303 This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration.

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“…[36][37][38] These factors might potentially affect the differentiation of surface ectoderm and mesoderm during embryonic eye development. Moreover, a recent study found that nicotine could induce CpG methylation of a PAX6-binding motif, and thus inhibit downstream steroid hormone production essential to antiinflammatory effect and fetal development; 10 this might potentially correlate to the PAX6 loss identified by Li et al 39 However, the exact mechanisms still remain unknown and need to be further investigated. Paternal smoking might also genetically affect sperm; 29 although little evidence is provided for this possible mechanism, it may offer a pathway to further investigate the genetic factors for ED in the future.…”

Section: Discussionmentioning

confidence: 98%

“…Paired Box 6 (PAX6) is a transcription factor that plays a key role in limbal stem cells and corneal epithelial fate determination and maintenance. 7,8 A recent study showed that PAX6 was completely absent from corneal dermoid tissue, suggesting its association with the pathogenesis of corneal dermoids, a subtype of ED; 9 nicotine is a potential environmental factor associated with this PAX6 absence. 10 Concerning genetic factors, most ED cases are considered sporadic.…”

Section: Introductionmentioning

confidence: 99%

The association of maternal factors with epibulbar dermoid of newborn: a retrospective, matched case–control study

Fan

et al. 2017

Eye

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PurposeTo determine the association of maternal factors and exposure during pregnancy with the incidence in newborns of epibulbar dermoid (ED), a congenital ocular surface benign tumor.Patients and methodsThis is a retrospective, paired case-control study in which 121 children with ED (case group) and 121 children without ED (control group) were recruited. Questionnaire-based interviews with mothers of participants were performed and maternal medical records during pregnancy were reviewed. The questionnaire investigated basic information, personal history, environmental exposure, exposure to maternal diseases, symptoms and corresponding medical treatments during pregnancy, and parental socioeconomic status. The case and control participants were matched for sex, birth weight, gestational age, and parental socioeconomic status level. Univariate and multivariate logistic regression analyses were conducted with ED as the main outcome variable.ResultsFactors significantly associated with ED were: history of maternal inevitable miscarriage (odds ratio (OR), 2.59; 95% confidence intervals (CI), 1.13-5.90), common cold in the first trimester (OR, 3.94; CI, 1.74-8.93), and paternal smoke exposure >half a pack per day during pregnancy (OR, 4.81; CI, 1.74-13.28).ConclusionHistory of maternal miscarriage, common cold exposure in the first trimester, and paternal smoking (>half a pack per day) during pregnancy could result in significant risk factors for ED of newborns. These data also imply that paternal smoking delivers nicotine to maternal respiratory system and uterine microenvironment that may both affect microvascular development and predispose the fetus to future ED.

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Transcription Factor PAX6 (Paired Box 6) Controls Limbal Stem Cell Lineage in Development and Disease

Cited by 59 publications

References 29 publications

Salivary gland stem cells: A review of development, regeneration and cancer

Salivary gland stem cells: A review of development, regeneration and cancer

Limbal stem cells: identity, developmental origin, and therapeutic potential

The association of maternal factors with epibulbar dermoid of newborn: a retrospective, matched case–control study

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