Propagation of human prostate tissue from induced pluripotent stem cells

Hepburn, Anastasia C.; Curry, Emma L; Moad, Mohammad; Steele, R.E.; Franco, Omar E.; Wilson, Laura; Singh, Parmveer; Buskin, Adriana; Crawford, Susan E.; Gaughan, Luke; Mills, Ian G.; Hayward, Simon W.; Robson, Craig; Heer, Rakesh

doi:10.1002/sctm.19-0286

Cited by 26 publications

(23 citation statements)

References 55 publications

(69 reference statements)

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“…In this example, it is important to note that organoids formed only from enterocytes have a spherical lumen, which indicates a correlation between differentiation and shape [66]. Though a vast majority of organoids form a spherical lumen, the structure of the epithelium lining the lumen can be different: either a monolayer of squamous or cuboidal cells (lung alveoli [7]), simple columnar (intestinal [30]), pseudostratified (lung airway spheres [3,8]), bilayered (prostate [41][42][43][44][45][46][47]), or stratified (cuboidal, columnar, or squamous). An extreme and unusual type of lumen is found in the pancreas.…”

Section: What Type Of Order Emerges?mentioning

confidence: 99%

“…An important difference of organoids from organs found in vivo is the limited complexity of shapes and their usually isotropic nature. Though there are a few examples of tube Table S1 formation [41], many intestinal organs normally forming tubes form spheres instead. Although the pancreas is an elongated organ, progenitors form roughly isotropic pancreatic organoids [22].…”

Section: What Type Of Order Emerges?mentioning

confidence: 99%

“…These pioneering studies have paved the way for many others which combine selforganization and control by media components-often chosen based on the knowledge of signaling pathways used in development and homeostasis. In this review, we will focus on endoderm-derived organoids such as lungs and trachea [3][4][5][6][7][8][9][10], liver [11][12][13][14][15][16][17], bile duct [18][19][20][21], pancreas [22][23][24][25][26], intestine [2,[27][28][29][30][31][32], esophagus [33][34][35], stomach [36][37][38][39][40], prostate [41][42][43][44][45][46][47], salivary gland [48][49]…”

Section: Introductionmentioning

confidence: 99%

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Self-organization of organoids from endoderm-derived cells

et al. 2020

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Organoids constitute biological systems which are used to model organ development, homeostasis, regeneration, and disease in vitro and hold promise for use in therapy. Reflecting in vivo development, organoids form from tissue cells or pluripotent stem cells. Cues provided from the media and individual cells promote self-organization of these uniform starting cells into a structure, with emergent differentiated cells, morphology, and often functionality that resemble the tissue of origin. Therefore, organoids provide a complement to two-dimensional in vitro culture and in vivo animal models of development, providing the experimental control and flexibility of in vitro methods with the three-dimensional context of in vivo models, with fewer ethical restraints than human or animal work. However, using organoids, we are only just beginning to understand on the cellular level how the external conditions and signaling between individual cells promote the emergence of cells and structures. In this review, we focus specifically on organoids derived from endodermal tissues: the starting conditions of the cells, signaling mechanisms, and external media that allow the emergence of higher order self-organization.

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Section: What Type Of Order Emerges?mentioning

confidence: 99%

Section: What Type Of Order Emerges?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Self-organization of organoids from endoderm-derived cells

et al. 2020

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“…CC-BY 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made The copyright holder for this preprint this version posted December 14, 2020. ; https://doi.org/10.1101/2020.12.13.422586 doi: bioRxiv preprint mesenchyme by 12 weeks can comprehensively generate prostate tissue with epithelial architecture, including cells at different differentiation stages of basal and luminal cells as well as neuroendocrine cells 49 .…”

Section: Emt Markersmentioning

confidence: 99%

Characterization of FGFR signaling in prostate cancer stem cells and inhibition via TKI treatment

Meyer

Haas

et al. 2020

Preprint

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BackgroundMetastatic castrate-resistant prostate cancer (CRPC) remains uncurable and novel therapies are needed to better treat patients. Aberrant Fibroblast Growth Factor Receptor (FGFR) signaling has been implicated in advanced prostate cancer (PCa), and FGFR1 is suggested to be a promising therapeutic target along with current androgen deprivation therapy.MethodsWe established a novel in vitro 3D culture system to study endogenous FGFR signaling in a rare subpopulation of prostate cancer stem cells (CSCs) in the cell lines PC3, DU145, LNCaP, and the induced pluripotent iPS87 cell line.Results3D-propagation of PCa cells generated spheroids with increased stemness markers ALDH7A1 and OCT4, while inhibition of FGFR signaling by BGJ398 or Dovitinib decreased cell survival and proliferation of 3D spheroids. The 3D spheroids exhibited altered expression of EMT markers associated with metastasis such as E-cadherin, vimentin and Snail, compared to 2D monolayer cells. TKI treatment did not result in significant changes of EMT markers, however, specific inhibition of FGFR signaling by BGJ398 showed more favorable molecular-level changes than treatment with the multi-RTK inhibitor Dovitinib.ConclusionsThis study provides evidence for the first time that FGFR1 plays an essential role in the proliferation of PCa CSCs at a molecular and cellular level, and suggests that TKI targeting of FGFR signaling may be a promising strategy for AR-independent CRPC.

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“…In our first Featured Article published this month in Stem Cells Translational Medicine, Hepburn et al report on the efficient in vitro differentiation of prostate-derived induced pluripotent stem cells (iPSCs) into prostate organoids that fully recapitulate prostate histology and cell type-content. 4 In a Related Article published recently in Stem Cells, Yin et al described how the loss of monoamine oxidase (MAO) expression in mice prompted a reduction in stem-like markers in prostate stem cells and the development of smaller atrophied prostates. 5 The pseudostratified epithelium of the human bronchial airway comprises a luminal layer containing the differentiated mucus-secreting and ciliated cells and a basal layer containing the bronchial stem cells.…”

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confidence: 99%

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Atkinson

2020

Stem Cells Translational Medicine

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The prostate, an exocrine gland of the male reproductive system, secretes a fluid that enhances sperm motility, prolongs sperm survival, and protects the genetic material contained within. Prostate enlargement due to nonmalignant hyperplasia is a common condition in older men, while prostate cancer represents one of the most common cancers in men in the West, as well as a significant cause of death. The in vitro modeling of the normal and diseased prostate through advanced three-dimensional (3D) culture techniques aims to explore

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Propagation of human prostate tissue from induced pluripotent stem cells

Cited by 26 publications

References 55 publications

Self-organization of organoids from endoderm-derived cells

Self-organization of organoids from endoderm-derived cells

Characterization of FGFR signaling in prostate cancer stem cells and inhibition via TKI treatment

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