Label-retaining Cells in the Rat Submandibular Gland

Overview

Journal J Histochem Cytochem

Publisher Sage Publications

Specialty Biochemistry

Date 2007 Sep 19

PMID 17875657

Citations 21

Authors

Masaya Kimoto

Yoshiaki Yura

Mitsunobu Kishino

Satoru Toyosawa

Yuzo Ogawa

Affiliations

Soon will be listed here.

Abstract

To identify stem cells in salivary glands, label-retaining cells (LRCs) were established in rat submandibular glands. Developing and regenerating glands were labeled with bromodeoxyuridine (BrdU). To cause gland regeneration, the glands were injured by duct obstruction. BrdU LRCs were observed in all the parenchymal structures except for the acinus of the glands labeled during regeneration. Among these LRCs, a few, but not many, expressed neither keratin18 (K18; an acinar/duct cell marker) nor alpha-smooth muscle actin (alphaSMA; a myoepithelial cell marker), and thus were putative stem cells. These (K18 and alphaSMA)(neg) LRCs were invariably observed in the intercalated duct and the excretory duct. In the intercalated duct, they were at the proximal end bordering the acinus (the neck of the intercalated duct). Next, to test the above identification, gland extirpation experiments were performed. LRCs were established by labeling developing glands with iododeoxyuridine (IdU) in place of BrdU. Removal of one submandibular gland forced the IdU-LRCs in the remaining gland to divide. They were labeled with chlorodeoxyuridine (CldU). The (K18 and alphaSMA)(neg) LRCs in the neck of the intercalated duct and in the excretory duct did not change in number or in IdU label. The CldU label appeared in these cells and then disappeared. These results indicate that the (K18 and alphaSMA)(neg) LRCs have divided asymmetrically and are thus considered salivary gland stem cells.

Citing Articles

Role of quiescent cells in the homeostatic maintenance of the adult submandibular salivary gland.

Serrano Martinez P, Maimets M, Bron R, van Os R, de Haan G, Pringle S iScience. 2022; 25(10):105047.

PMID: 36147959 PMC: 9485076. DOI: 10.1016/j.isci.2022.105047.

Aldehyde dehydrogenase 3A1 deficiency leads to mitochondrial dysfunction and impacts salivary gland stem cell phenotype.

Viswanathan V, Cao H, Saiki J, Jiang D, Mattingly A, Nambiar D PNAS Nexus. 2022; 1(2):pgac056.

PMID: 35707206 PMC: 9186046. DOI: 10.1093/pnasnexus/pgac056.

Building a Functional Salivary Gland for Cell-Based Therapy: More than Secretory Epithelial Acini.

Barrows C, Wu D, Farach-Carson M, Young S Tissue Eng Part A. 2020; 26(23-24):1332-1348.

PMID: 32829674 PMC: 7759264. DOI: 10.1089/ten.TEA.2020.0184.

Concise Review: A Critical Evaluation of Criteria Used to Define Salivary Gland Stem Cells.

Weng P, Aure M, Ovitt C Stem Cells. 2019; 37(9):1144-1150.

PMID: 31175700 PMC: 6711783. DOI: 10.1002/stem.3046.

Diverse progenitor cells preserve salivary gland ductal architecture after radiation-induced damage.

May A, Cruz-Pacheco N, Emmerson E, Gaylord E, Seidel K, Nathan S Development. 2018; 145(21).

PMID: 30305288 PMC: 6240316. DOI: 10.1242/dev.166363.

References

Potten C, Booth C, Hargreaves D . The small intestine as a model for evaluating adult tissue stem cell drug targets. Cell Prolif. 2003; 36(3):115-29. PMC: 6496932. DOI: 10.1046/j.1365-2184.2003.00264.x. View

Man Y, Ball W, Marchetti L, Hand A . Contributions of intercalated duct cells to the normal parenchyma of submandibular glands of adult rats. Anat Rec. 2001; 263(2):202-14. DOI: 10.1002/ar.1098. View

Ogawa Y . Immunocytochemistry of myoepithelial cells in the salivary glands. Prog Histochem Cytochem. 2003; 38(4):343-426. DOI: 10.1016/s0079-6336(03)80001-3. View

Ogawa Y, Kishino M, Atsumi Y, Kimoto M, Fukuda Y, Ishida T . Plasmacytoid cells in salivary-gland pleomorphic adenomas: evidence of luminal cell differentiation. Virchows Arch. 2003; 443(5):625-34. DOI: 10.1007/s00428-003-0890-3. View

Smalley M, Ashworth A . Stem cells and breast cancer: A field in transit. Nat Rev Cancer. 2003; 3(11):832-44. DOI: 10.1038/nrc1212. View

Takahashi S, Shinzato K, Nakamura S, Domon T, Yamamoto T, Wakita M . Cell death and cell proliferation in the regeneration of atrophied rat submandibular glands after duct ligation. J Oral Pathol Med. 2003; 33(1):23-9. DOI: 10.1111/j.1600-0714.2004.00191.x. View

Maslov A, Barone T, Plunkett R, Pruitt S . Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice. J Neurosci. 2004; 24(7):1726-33. PMC: 6730468. DOI: 10.1523/JNEUROSCI.4608-03.2004. View

Tamarin A . Submaxillary gland recovery from obstruction. I. Overall changes and electron microscopic alterations of granular duct cells. J Ultrastruct Res. 1971; 34(3):276-87. DOI: 10.1016/s0022-5320(71)80072-2. View

Hanks C, CHAUDHRY A . Regeneration of rat submandibular gland following partial extirpation. A light and electron microscopic study. Am J Anat. 1971; 130(2):195-207. DOI: 10.1002/aja.1001300206. View

10.

Eversole L . Histogenic classification of salivary tumors. Arch Pathol. 1971; 92(6):433-43. View

11.

Chang W . Cell population changes during acinus formation in the postnatal rat submandibular gland. Anat Rec. 1974; 178(2):187-201. DOI: 10.1002/ar.1091780204. View

12.

Cairns J . Mutation selection and the natural history of cancer. Nature. 1975; 255(5505):197-200. DOI: 10.1038/255197a0. View

13.

Srinivasan R, Chang W . The development of the granular convoluted duct in the rat submandibular gland. Anat Rec. 1975; 182(1):29-39. DOI: 10.1002/ar.1091820104. View

14.

Alvares E, Sesso A . Cell proliferation, differentiation and transformation in the rat submandibular gland during early postnatal growth. A quantitative and morphological study. Arch Histol Jpn. 1975; 38(3):177-208. DOI: 10.1679/aohc1950.38.177. View

15.

Regezi J, BATSAKIS J . Histogenesis of salivary gland neoplasms. Otolaryngol Clin North Am. 1977; 10(2):297-307. View

16.

LAJTHA L . Stem cell concepts. Differentiation. 1979; 14(1-2):23-34. DOI: 10.1111/j.1432-0436.1979.tb01007.x. View

17.

Bickenbach J . Identification and behavior of label-retaining cells in oral mucosa and skin. J Dent Res. 1981; 60 Spec No C:1611-20. DOI: 10.1177/002203458106000311011. View

18.

Yagil C, Michaeli Y, Zajicek G . Compensatory proliferative response of the rat submandibular salivary gland to unilateral extirpation. Virchows Arch B Cell Pathol Incl Mol Pathol. 1985; 49(1):83-91. DOI: 10.1007/BF02912087. View

19.

Zajicek G, Yagil C, Michaeli Y . The streaming submandibular gland. Anat Rec. 1985; 213(2):150-8. DOI: 10.1002/ar.1092130206. View

20.

Potten C . Cell cycles in cell hierarchies. Int J Radiat Biol Relat Stud Phys Chem Med. 1986; 49(2):257-78. DOI: 10.1080/09553008514552541. View