NTPDase2+ Cells Generate Lingual Epithelia and Papillae

Li, Feng; Cao, Jie; Zhou, Mingliang

doi:10.3389/fgene.2012.00255

Cited by 8 publications

(14 citation statements)

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“…Our previous study suggested the presence of a cell migration stream consisting of multiple stem cell pools and differentiated cell pools in the lingual epithelia. The local microenviroment plays an important role in regulating cell differentiation/development in the lingual epithelia (Li et al, ; Li and Zhou, ). It has also been suggested that it is the position which determines whether a cell will specialize into one of two different alternate fates, and the final fate of the cell is based purely on the particular microenvironment the cell is forced by chance to occupy in the lingual epithelia.…”

Section: Resultsmentioning

confidence: 99%

Conditional expression of the dominant‐negative TGF‐β receptor type II elicits lingual epithelial hyperplasia in transgenic mice

Zhou

2013

Developmental Dynamics

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Background: The transforming growth factor-b (TGF-b) signaling pathway is generally believed to be a potent inhibitor of proliferation. However, many epithelia lacking the essential Tgfbr2 gene still maintain normal tissue homeostasis. Here, transgenic mice expressing rtTA from the human keratin 14 (K14) promoter were used to generate an inducible dominant-negative TGF-b receptor type II (Tgfbr2) mutant model, which allowed us to distinguish between the primary and secondary effects of TGF-b signaling disruption by Doxycycline treatment in K141 epithelial stem cells. Results: We showed that in mice lacking TGF-b signaling in K141 cells, invasive carcinomas developed on the ventral surface of the tip of the tongue, while filiform papillae on the dorsal surface showed different pathological changes from the tip to the posterior of the tongue. In addition, acetylation levels of histone H4 and histone H3 rapidly increased, while pMAPK activity was enhanced and Jagged2 inactivated in lingual epithelia after disruption of TGF-b signaling. Mice lacking TGF-b signaling in K141 cells during 35 days of TGF-b signaling disruption develop invasive carcinoma on the ventral surface of the tip of the tongue, while filiform papillae on the dorsal surface show different pathological changes from the tip to the posterior of the tongue. Acetylation levels of histone H4 and histone H3 rapidly increase in the tip of the tongue after disruption of TGF-b signaling. pMAPK activity is enhanced and Jagged2 inactivated in lingual epithelia after 3 days of TGF-b signaling disruption.

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Section: Resultsmentioning

confidence: 99%

Conditional expression of the dominant‐negative TGF‐β receptor type II elicits lingual epithelial hyperplasia in transgenic mice

Zhou

2013

Developmental Dynamics

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“…In a previous study, we generated NTPDase2‐rtTA transgenic mice. Using double‐ and triple‐crossed mice, NTPDase2 was shown to be expressed in lingual epithelia and papillae . In order to study further the characteristics of NTPDase2+ cells, we crossed the NTPDase2‐rtTA transgenic mice with TeTO‐DTA transgenic mice to create a double transgenic NTPDase2‐rtTA‐TeTO‐DTA mice (Figure A).…”

Section: Resultsmentioning

confidence: 99%

“…The expression construct was generated by cloning the rtTA gene and its polyadenylation signal into RP23‐47P18 (http://bacpac.chori.org), replacing the coding sequence of NTPDase2, using the Red recombination system. Transgenic lines were produced by pronuclear injection of zygotes from C57BL/6 mice using the modified RP23‐47P18 . TetO‐DTA animals (No 008468) were obtained from Jackson Laboratories (Bar Harbor, ME, USA).…”

Section: Methodsmentioning

confidence: 99%

“…As previously mentioned, a genetic mapping model has shown that NTPDase2+ cells contribute to the formation of filiform papillae, generate the taste bud cells, and produce lingual epithelia . Given that NTPDase2+ cells are involved in the formation of stem cell pools in lingual epithelia and papillae, the next question is what kind of pathological changes will be observed after ablation of NTPDase2+ cells.…”

Section: Introductionmentioning

confidence: 98%

“…Recently, based on our previous results using mutation of TGF‐β signaling in K14+ and NTPDase2+ cells, a developmental model has been suggested for lingual epithelia and papillae. There are multiple stem cell pools in lingual epithelia and papillae consisting of stem cells pools, TA cell pools and differentiated cell pools . Like K14+ cells, NTPDase2+ cells are also a type of stem cell, responsible for generating lingual epithelia and papillae (including fungiform papillae, filiform papillae and taste bud cells) …”

Section: Introductionmentioning

confidence: 99%

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Ablation of NTPDase2+ cells inhibits the formation of filiform papillae in tongue tip

Niu

Zhu

2018

Anim Models and Exp Med

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Background Lingual epithelia in the tongue tip are among the most rapidly regenerating tissues, but the mechanism of cell genesis in this tissue is still unknown. Previous study has suggested the existence of multiple stem cell pools in lingual epithelia and papillae. Like K14+ and Sox2+ cells, NTPD ase2+ cells have characteristics of stem cells. Methods We employed a system using doxycycline to conditionally ablate NTPD ase2+ cells in lingual epithelia and papillae by regulated expression of the diphtheria toxin A ( DTA ) gene. Transgenic lines, which expressed the rt TA gene in NTPD ase2+ cells, were produced by pronuclear injection of zygotes from C57 BL /6 mice using the BAC clone RP 23‐47P18. The NTPD ase2‐rt TA transgenic mice were crossed with the TetO‐ DTA transgenic animals. The double transgenic mice were treated with doxycycline. Doxycycline (Dox) was diluted in 5% sucrose in water to a final concentration of 0.3‐0.5 mg/mL and supplied as drinking water. Results After 15 days of Dox induction, the expression of NTPD ase2, Sox2 and K14 was ablated from lingual epithelia. DTA expression in NTPD ase2+ cells did not inhibit the turnover of GNAT 3+ or PLC β2+ cells in taste buds, nor the expression of S100β beneath lingual epithelia and papillae. After 35 days ablation of NTPD ase2+ cells, the basic structure of lingual epithelia and papillae remained intact. However, the ratio of cell to total tissue area was decreased in lingual epithelia and circumvallate ( CV ) papillae. DTA expression also inhibited the regeneration of filiform papillae on the dorsal surface of the tongue tip. Conclusions These studies provide important insights into the understanding of dynamic equilibrium among the multiple stem cell populations present in the lingual epithelia and papillae.

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Development of a humanized HLA‐A30 transgenic mouse model

Zhu

Niu

Liu

et al. 2022

Anim Models and Exp Med

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Background: There are remarkable genetic differences between animal major histocompatibility complex (MHC) systems and the human leukocyte antigen (HLA) system. HLA transgenic humanized mouse model systems offer a much better method to study the HLA-A-related principal mechanisms for vaccine development and HLA-Arestricted responses against infection in human. Methods: A recombinant gene encoding the chimeric HLA-A30 monochain was constructed. This HHD molecule contains the following: α1-α2 domains of HLA-A30, α3 and cytoplasmic domains of H-2D b , linked at its N-terminus to the C-terminus of human β2m by a 15-amino-acid peptide linker. The recombinant gene encoding the chimeric HLA-A30 monochain cassette was introduced into bacterial artificial chromosome (BAC) CH502-67J3 containing the HLA-A01 gene locus by Red-mediated homologous recombination. Modified BAC CH502-67J3 was microinjected into the pronuclei of wild-type mouse oocytes. This humanized mouse model was further used to assess the immune responses against influenza A virus (H1N1) pdm09 clinically isolated from human patients. Immune cell population, cytokine production, and histopathology in the lung were analyzed. Results: We describe a novel human β2m-HLA-A30 (α1α2)-H-2D b (α3 transmembrane cytoplasmic) (HHD) monochain transgenic mouse strain, which contains the intact HLA-A01 gene locus including 49 kb 5′-UTR and 74 kb 3′-UTR of HLA-A01*01. Five transgenic lines integrated into the large genomic region of HLA-A gene locus were obtained, and the robust expression of exogenous transgene was detected in various tissues from A30-18# and A30-19# lines encompassing the intact flanking sequences. Flow cytometry revealed that the introduction of a large genomic region in HLA-A gene locus can influence the immune cell constitution in humanized mice. Pdm09 infection caused a similar immune response among HLA-A30 Tg humanized mice and wild-type mice, and induced the rapid increase of cytokines, including IFNγ, TNFα, and IL-6, in both HLA-A30 humanized Tg mice and wild-type mice. The expression of This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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NTPDase2+ Cells Generate Lingual Epithelia and Papillae

Cited by 8 publications

References 53 publications

Conditional expression of the dominant‐negative TGF‐β receptor type II elicits lingual epithelial hyperplasia in transgenic mice

Conditional expression of the dominant‐negative TGF‐β receptor type II elicits lingual epithelial hyperplasia in transgenic mice

Ablation of NTPDase2+ cells inhibits the formation of filiform papillae in tongue tip

Development of a humanized HLA‐A30 transgenic mouse model

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