Differentiation of Human Induced Pluripotent Stem Cells into a Keratinocyte Lineage

Kogut, Igor; Roop, Dennis R.; Bilousova, Ganna

doi:10.1007/7651_2013_64

Cited by 39 publications

(38 citation statements)

References 23 publications

(19 reference statements)

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“…Depending on the application, either skin biopsies, primary cells or cell lines can be used [66,68,69]. Also, human induced pluripotent stem cells provide a source to mimic healthy and diseased skin models as they can be differentiated into keratinocytes [70], fibroblasts [71], melanocytes [72] and endothelial cells [67]. Besides simplified models with dermis and epidermis, also more complex models with hair follicles and adipocytes [73], immune cells [74] and features resembling sweat gland pores [75] exist.…”

Section: Organ-on-a-chipmentioning

confidence: 99%

“…Nonetheless, it was shown that human iPSC provide a source to mimic healthy skin models as they can be differentiated into keratinocytes [70], fibroblasts [71], melanocytes [72], and endothelial cells [67]. Disease models can be generated with iPSCs derived from somatic cells having a genetic mutation.…”

Section: Outlook: Skin Organoids and Their Potential Use For Personalmentioning

confidence: 99%

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In vitro skin three-dimensional models and their applications

Klicks

Molitor

Ertongur-Fauth

et al. 2017

JCB

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Abstract. Skin fulfils a plethora of eminent physiological functions ranging from physical barrier over immunity shield to the interface mediating social interaction. Prone to several acquired and inherited diseases, skin is therefore a major target of pharmaceutical and cosmetic research. The lack of similarity between human and animal skin and rising ethical concerns in the use of animal models have driven the search for novel realistic three-dimensional skin models. This review provides a survey of contemporary skin models and compares them in terms of applicability, reliability, cost and complexity.Keywords: Skin, phenotypic screening, 3D models, pharmaceutical research Skin -composition and functionHuman skin covers an area of almost 2 m 2 in the adult and consists of the three major layers, subcutis, dermis, and epidermis. The subcutis is composed of adipose and epithelial cells. It harbours blood vessels, neurites of peripheral neurons, Vater-Pacini mechanosensors, and, partially, also sweat glands and hair follicles. It connects the skin to periosteum and fascia, absorbs forces, and mediates thermal insulation. The dermis supplies the epidermis with mechanical support and nutrients. It is stratified into an inner, reticular, and an outer, papillary, zone. The dermis houses most sebaceous glands, sweat glands, hair follicles, smooth muscle cells, and capillary beds and, thus, regulates skin moisture, body temperature, and performs the secretory function of skin. The papillary layer is characterized by relatively loose connective tissue, where Meissner corpuscles sense touch. Immune cells, particularly mast cells and dendritic cells, are patrolling in the papillary layer and mediate local inflammatory reactions and immune surveillance. Finally, dermal fibroblasts secrete extracellular matrix (ECM) and basement membrane components. These are primarily collagens I and III, and a proteoglycan-rich ground substance [1]. The resulting ECM mediates tensile strength of the dermis. The dermo-epidermal junction is centered around a special basement membrane. This is composed of a laminin/collagen IV scaffold and further typical basement membrane components such as perlecans and nidogens [1].The epidermis is a squamous epithelium of 50-100 m thickness. It is devoid of blood vessels but contains keratinocytes, Merkel cell mechanosensors, Langerhans immune cells, and melanocytes. The 1 These authors contributed equally.

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Section: Organ-on-a-chipmentioning

confidence: 99%

Section: Outlook: Skin Organoids and Their Potential Use For Personalmentioning

confidence: 99%

In vitro skin three-dimensional models and their applications

Klicks

Molitor

Ertongur-Fauth

et al. 2017

JCB

View full text Add to dashboard Cite

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“…We previously reported that progenitors of epidermal keratinocytes were generated from human induced pluripotent stem cells (PSCs) (Hayashi et al, , ). In addition, there have been some reports of keratinocyte lineages being induced from mouse (Bilousova & Roop, ) and human (Kogut, Roop, & Bilousova, ) induced PSCs. However, induction of induced PSCs into site‐specific epidermal keratinocytes has not been reported thus far.…”

Section: Introductionmentioning

confidence: 99%

Use of homeobox gene expression patterns to determine anatomical regions of origin for body surface tissues derived from adult mice

Okubo

Hayashi

Shibata

et al. 2018

J Tissue Eng Regen Med

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Anatomical regions of the skin have distinct functions and anatomical characteristics, including thicker or thinner epidermis, more or fewer hair follicles, and lighter or darker skin. For a better therapeutic outcome of skin transplantation, site-specific characteristics of grafted tissues need to be taken into account in terms of their functionality and beauty. However, there is no method for evaluating positional information of epidermal cells. Homeobox genes are expressed along the anterior-posterior axis and direct the body plan in the animal development process. Although the expression of several HOX genes is known to be retained as the positional information in adult tissue, their expression patterns in the body surface tissues in adult mammals are still incompletely understood. In this study, we investigated the expression patterns of 40 homeobox genes, including 39 Hox genes and the paired box 6 (Pax6) gene, in body surface tissues of adult mice. On the basis of the results obtained, we proposed, for the first time, a method for determining anatomical regions of origin for body surface tissues derived from adult mice using Hox genes and Pax6. Evaluation of expression levels of at least 7 Hox genes and Pax6 should be sufficient to distinguish 11 anatomical body surface tissues derived from the adult mouse body. The proposed method may be useful not only for determining the origin of surface tissues from specific anatomical regions of the mammalian body but also for predicting positional information of epithelial cells generated from pluripotent stem cells.

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“…Epidermal organotypic “raft” cultures, grown on an air-medium interface, were originally developed in the 1980s as an ex vivo approach for understanding human skin function (Asselineau and Prunieras 1984; Prunieras, Regnier and Woodley 1983) and continue to provide an important alternative to animal models (Getsios, Simpson, Kojima, Harmon, Sheu, Dusek et al 2009). The cultures are typically generated using primary keratinocytes isolated from readily available human foreskins; however, adult keratinocytes and keratinocytes derived from iPS cells (Bilousova and Roop 2013; Kogut, Roop and Bilousova 2014) are emerging as additional cell sources. These isolated keratinocytes can be passaged multiple times in culture and genetically manipulated using viral vectors or RNAi.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Model of the Epidermis

Arnette

Koetsier

Hoover

et al. 2016

Methods in Enzymology

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Overview Much of our understanding of the biological processes that underlie cellular functions in humans, such as cell-cell communication, intracellular signaling, and transcriptional and post-transcriptional control of gene expression, has been acquired from studying cells in a two-dimensional (2D) tissue culture environment. However, it has become increasingly evident that the 2D environment does not support certain cell functions. The need for more physiologically relevant models prompted the development of three-dimensional (3D) cultures of epithelial, endothelial and neuronal tissues (Shamir and Ewald 2014). These models afford investigators with powerful tools to study the contribution of spatial organization, often in the context of relevant extracellular matrix and stromal components, to cellular and tissue homeostasis in normal and disease states.

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Differentiation of Human Induced Pluripotent Stem Cells into a Keratinocyte Lineage

Cited by 39 publications

References 23 publications

In vitro skin three-dimensional models and their applications

In vitro skin three-dimensional models and their applications

Use of homeobox gene expression patterns to determine anatomical regions of origin for body surface tissues derived from adult mice

In Vitro Model of the Epidermis

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