Defining the Localization and Molecular Characteristic of Minor Salivary Gland Label-retaining Cells

Overview

Journal Stem Cells

Publisher Oxford University Press

Specialties Cell Biology
Reproductive Medicine

Date 2014 Apr 10

PMID 24715701

Citations 10

Authors

Hongjun Zhang

Keerthi Boddupally

Eve Kandyba

Krzysztof Kobielak

Yibu Chen

Sutao Zu

Rashi Krishnan

Uttam Sinha

Agnieszka Kobielak

Affiliations

Soon will be listed here.

Abstract

Adult stem cells (SCs) are important to maintain homeostasis of tissues including several mini-organs like hair follicles and sweat glands. However, the existence of stem cells in minor salivary glands (SGs) is largely unexplored. In vivo histone2B green fluorescent protein pulse chase strategy has allowed us to identify slow-cycling, label-retaining cells (LRCs) of minor SGs that preferentially localize in the basal layer of the lower excretory duct with a few in the acini. Engraftment of isolated SG LRC in vivo demonstrated their potential to differentiate into keratin 5 (basal layer marker) and keratin 8 (luminal layer marker)-positive structures. Transcriptional analysis revealed activation of TGFβ1 target genes in SG LRC and BMP signaling in SG progenitors. We also provide evidence that minor SGSCs are sensitive to tobacco-derived tumor-inducing agent and give rise to tumors resembling low grade adenoma. Our data highlight for the first time the existence of minor SG LRCs with stem cells characteristic and emphasize the role of transforming growth factor beta (TGFβ) pathway in their maintenance.

Citing Articles

Maintenance of adult stem cells from human minor salivary glands via the Wnt signaling pathway.

Kang B, Zhu Z, Wang J, Zhou J, Yu S, Zhou X Stem Cell Res Ther. 2023; 14(1):220.

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Autologous mesenchymal stem cells offer a new paradigm for salivary gland regeneration.

Marinkovic M, Tran O, Wang H, Abdul-Azees P, Dean D, Chen X Int J Oral Sci. 2023; 15(1):18.

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Thermoresponsive fiber-based microwells capable of formation and retrieval of salivary gland stem cell spheroids for the regeneration of irradiation-damaged salivary glands.

Hong H, Cho J, Yoon Y, Choi D, Lee S, Lee H J Tissue Eng. 2022; 13:20417314221085645.

PMID: 35422983 PMC: 9003645. DOI: 10.1177/20417314221085645.

Origin and Lineage Plasticity of Endogenous Lacrimal Gland Epithelial Stem/Progenitor Cells.

Basova L, Parfitt G, Richardson A, Delcroix V, Umazume T, Pelaez D iScience. 2020; 23(6):101230.

PMID: 32559730 PMC: 7303985. DOI: 10.1016/j.isci.2020.101230.

Phenotypic Analysis of BrdU Label-Retaining Cells during the Maturation of Conducting Airway Epithelium in a Porcine Lung.

Jia Y, You X, Ma N, Li H, Liu G, Wang Y Stem Cells Int. 2019; 2019:7043890.

PMID: 30936924 PMC: 6415319. DOI: 10.1155/2019/7043890.

References

Wang L, Liu Z, Gambardella L, Delacour A, Shapiro R, Yang J . Regular articles: conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration. J Invest Dermatol. 2000; 114(5):901-8. DOI: 10.1046/j.1523-1747.2000.00951.x. View

Ahn S, Joyner A . In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog. Nature. 2005; 437(7060):894-7. DOI: 10.1038/nature03994. View

Schwarz S, Rotter N . Human salivary gland stem cells: isolation, propagation, and characterization. Methods Mol Biol. 2012; 879:403-42. DOI: 10.1007/978-1-61779-815-3_25. View

Tumbar T, Guasch G, Greco V, Blanpain C, Lowry W, Rendl M . Defining the epithelial stem cell niche in skin. Science. 2003; 303(5656):359-63. PMC: 2405920. DOI: 10.1126/science.1092436. View

Nanduri L, Maimets M, Pringle S, van der Zwaag M, van Os R, Coppes R . Regeneration of irradiated salivary glands with stem cell marker expressing cells. Radiother Oncol. 2011; 99(3):367-72. DOI: 10.1016/j.radonc.2011.05.085. View

Peng Y, Levine C, Zahid S, Wilson E, Joyner A . Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration. Proc Natl Acad Sci U S A. 2013; 110(51):20611-6. PMC: 3870668. DOI: 10.1073/pnas.1315729110. View

Massague J . TGFbeta in Cancer. Cell. 2008; 134(2):215-30. PMC: 3512574. DOI: 10.1016/j.cell.2008.07.001. View

Zou P, Yoshihara H, Hosokawa K, Tai I, Shinmyozu K, Tsukahara F . p57(Kip2) and p27(Kip1) cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc70. Cell Stem Cell. 2011; 9(3):247-61. DOI: 10.1016/j.stem.2011.07.003. View

Scandura J, Boccuni P, Massague J, Nimer S . Transforming growth factor beta-induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation. Proc Natl Acad Sci U S A. 2004; 101(42):15231-6. PMC: 524079. DOI: 10.1073/pnas.0406771101. View

10.

Rheinwald J, Green H . Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature. 1977; 265(5593):421-4. DOI: 10.1038/265421a0. View

11.

Ferrer-Vaquer A, Piliszek A, Tian G, Aho R, Dufort D, Hadjantonakis A . A sensitive and bright single-cell resolution live imaging reporter of Wnt/ß-catenin signaling in the mouse. BMC Dev Biol. 2010; 10:121. PMC: 3017038. DOI: 10.1186/1471-213X-10-121. View

12.

Oshimori N, Fuchs E . The harmonies played by TGF-β in stem cell biology. Cell Stem Cell. 2012; 11(6):751-64. PMC: 3612991. DOI: 10.1016/j.stem.2012.11.001. View

13.

Guzzo M, Locati L, Prott F, Gatta G, McGurk M, Licitra L . Major and minor salivary gland tumors. Crit Rev Oncol Hematol. 2009; 74(2):134-48. DOI: 10.1016/j.critrevonc.2009.10.004. View

14.

Lombaert I, Brunsting J, Wierenga P, Faber H, Stokman M, Kok T . Rescue of salivary gland function after stem cell transplantation in irradiated glands. PLoS One. 2008; 3(4):e2063. PMC: 2329592. DOI: 10.1371/journal.pone.0002063. View

15.

Kandyba E, Leung Y, Chen Y, Widelitz R, Chuong C, Kobielak K . Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation. Proc Natl Acad Sci U S A. 2013; 110(4):1351-6. PMC: 3557042. DOI: 10.1073/pnas.1121312110. View

16.

Hu M, Hu G, Kim Y, Tsuji T, McBride J, Hinds P . Role of p12(CDK2-AP1) in transforming growth factor-beta1-mediated growth suppression. Cancer Res. 2004; 64(2):490-9. DOI: 10.1158/0008-5472.can-03-2284. View

17.

David R, Shai E, Aframian D, Palmon A . Isolation and cultivation of integrin alpha(6)beta(1)-expressing salivary gland graft cells: a model for use with an artificial salivary gland. Tissue Eng Part A. 2008; 14(2):331-7. DOI: 10.1089/tea.2007.0122. View

18.

Bullard T, Koek L, Roztocil E, Kingsley P, Mirels L, Ovitt C . Ascl3 expression marks a progenitor population of both acinar and ductal cells in mouse salivary glands. Dev Biol. 2008; 320(1):72-8. PMC: 2570651. DOI: 10.1016/j.ydbio.2008.04.018. View

19.

Pringle S, van Os R, Coppes R . Concise review: Adult salivary gland stem cells and a potential therapy for xerostomia. Stem Cells. 2013; 31(4):613-9. DOI: 10.1002/stem.1327. View

20.

Greco V, Chen T, Rendl M, Schober M, Pasolli H, Stokes N . A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell. 2009; 4(2):155-69. PMC: 2668200. DOI: 10.1016/j.stem.2008.12.009. View