Connexins in the Development and Physiology of Stem Cells

Overview

Journal Tissue Barriers

Specialties Anatomy & Histology
Biology
Physiology

Date 2021 Jul 6

PMID 34227910

Citations 4

Authors

Anaclet Ngezahayo

Frederike A Ruhe

Affiliations

Soon will be listed here.

Abstract

Connexins (Cxs) form gap junction (GJ) channels linking vertebrate cells. During embryogenesis, Cxs are expressed as early as the 4-8 cell stage. As cells differentiate into pluripotent stem cells (PSCs) and during gastrulation, the Cx expression pattern is adapted. Knockdown of Cx43 and Cx45 does not interfere with embryogenic development until the blastula stage, questioning the role of Cxs in PSC physiology and development. Studies in cultivated and induced PSCs (iPSCs) showed that Cx43 is essential for the maintenance of self-renewal and the expression of pluripotency markers. It was found that the role of Cxs in PSCs is more related to regulation of transcription or cell-cell adherence than to formation of GJ channels. Furthermore, a crucial role of Cxs for the self-renewal and differentiation was shown in cultivated adult mesenchymal stem cells. This review aims to highlight aspects that link Cxs to the function and physiology of stem cell development.

Citing Articles

Regulation of the gap junction interplay during postnatal development in the rat epididymis.

Cyr D, Adam C, Dufresne J, Gregory M Cell Tissue Res. 2024; 398(3):191-206.

PMID: 39412535 DOI: 10.1007/s00441-024-03919-1.

Intercellular Communication in Airway Epithelial Cell Regeneration: Potential Roles of Connexins and Pannexins.

Badaoui M, Chanson M Int J Mol Sci. 2023; 24(22).

PMID: 38003349 PMC: 10671439. DOI: 10.3390/ijms242216160.

Non-Coding RNAs as Biomarkers for Embryo Quality and Pregnancy Outcomes: A Systematic Review and Meta-Analysis.

Huang W, Chen A, Ng E, Yeung W, Lee Y Int J Mol Sci. 2023; 24(6).

PMID: 36982824 PMC: 10052053. DOI: 10.3390/ijms24065751.

Trans-Compartmental Regulation of Tight Junction Barrier Function.

Naser A, Lu Q, Chen Y Tissue Barriers. 2022; 11(4):2133880.

PMID: 36220768 PMC: 10606786. DOI: 10.1080/21688370.2022.2133880.

References

Klee P, Lamprianou S, Charollais A, Caille D, Sarro R, Cederroth M . Connexin implication in the control of the murine beta-cell mass. Pediatr Res. 2011; 70(2):142-7. DOI: 10.1203/PDR.0b013e318220f106. View

Sousa P, Valdimarsson G, Nicholson B, Kidder G . Connexin trafficking and the control of gap junction assembly in mouse preimplantation embryos. Development. 1993; 117(4):1355-67. DOI: 10.1242/dev.117.4.1355. View

Snykers S, Kock J, Tamara V, Rogiers V . Hepatic differentiation of mesenchymal stem cells: in vitro strategies. Methods Mol Biol. 2011; 698:305-14. DOI: 10.1007/978-1-60761-999-4_23. View

Conover J, Notti R . The neural stem cell niche. Cell Tissue Res. 2007; 331(1):211-24. DOI: 10.1007/s00441-007-0503-6. View

Kashyap V, Rezende N, Scotland K, Shaffer S, Persson J, Gudas L . Regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the NANOG, OCT4, and SOX2 pluripotency transcription factors with polycomb repressive complexes and stem cell microRNAs. Stem Cells Dev. 2009; 18(7):1093-108. PMC: 3135180. DOI: 10.1089/scd.2009.0113. View

Reaume A, Sousa P, Kulkarni S, Langille B, Zhu D, Davies T . Cardiac malformation in neonatal mice lacking connexin43. Science. 1995; 267(5205):1831-4. DOI: 10.1126/science.7892609. View

Barzilay R, Melamed E, Offen D . Introducing transcription factors to multipotent mesenchymal stem cells: making transdifferentiation possible. Stem Cells. 2009; 27(10):2509-15. DOI: 10.1002/stem.172. View

Lin F, Zheng G, Chang B, Chen R, Zhang Q, Xie P . Connexin 43 Modulates Osteogenic Differentiation of Bone Marrow Stromal Cells Through GSK-3beta/Beta-Catenin Signaling Pathways. Cell Physiol Biochem. 2018; 47(1):161-175. DOI: 10.1159/000489763. View

Elias L, Wang D, Kriegstein A . Gap junction adhesion is necessary for radial migration in the neocortex. Nature. 2007; 448(7156):901-7. DOI: 10.1038/nature06063. View

10.

Yancey S, Biswal S, REVEL J . Spatial and temporal patterns of distribution of the gap junction protein connexin43 during mouse gastrulation and organogenesis. Development. 1992; 114(1):203-12. DOI: 10.1242/dev.114.1.203. View

11.

Esseltine J, Shao Q, Brooks C, Sampson J, Betts D, Seguin C . Connexin43 Mutant Patient-Derived Induced Pluripotent Stem Cells Exhibit Altered Differentiation Potential. J Bone Miner Res. 2017; 32(6):1368-1385. DOI: 10.1002/jbmr.3098. View

12.

Kurtenbach S, Kurtenbach S, Zoidl G . Gap junction modulation and its implications for heart function. Front Physiol. 2014; 5:82. PMC: 3936571. DOI: 10.3389/fphys.2014.00082. View

13.

Togashi K, Kumagai J, Sato E, Shirasawa H, Shimoda Y, Makino K . Dysfunction in gap junction intercellular communication induces aberrant behavior of the inner cell mass and frequent collapses of expanded blastocysts in mouse embryos. J Assist Reprod Genet. 2015; 32(6):969-76. PMC: 4491087. DOI: 10.1007/s10815-015-0479-1. View

14.

Huettner J, Lu A, Qu Y, Wu Y, Kim M, McDonald J . Gap junctions and connexon hemichannels in human embryonic stem cells. Stem Cells. 2006; 24(7):1654-67. DOI: 10.1634/stemcells.2005-0003. View

15.

Rodriguez-Sinovas A, Ruiz-Meana M, Denuc A, Garcia-Dorado D . Mitochondrial Cx43, an important component of cardiac preconditioning. Biochim Biophys Acta Biomembr. 2017; 1860(1):174-181. DOI: 10.1016/j.bbamem.2017.06.011. View

16.

Krampera M, Marconi S, Pasini A, Galie M, Rigotti G, Mosna F . Induction of neural-like differentiation in human mesenchymal stem cells derived from bone marrow, fat, spleen and thymus. Bone. 2006; 40(2):382-90. DOI: 10.1016/j.bone.2006.09.006. View

17.

Dermietzel R, Gao Y, Scemes E, Vieira D, Urban M, Kremer M . Connexin43 null mice reveal that astrocytes express multiple connexins. Brain Res Brain Res Rev. 2000; 32(1):45-56. DOI: 10.1016/s0165-0173(99)00067-3. View

18.

Oyamada M, Takebe K, Endo A, Hara S, Oyamada Y . Connexin expression and gap-junctional intercellular communication in ES cells and iPS cells. Front Pharmacol. 2013; 4:85. PMC: 3699729. DOI: 10.3389/fphar.2013.00085. View

19.

Cheng Y, Dong J, Bian Q . Small molecules for mesenchymal stem cell fate determination. World J Stem Cells. 2019; 11(12):1084-1103. PMC: 6904864. DOI: 10.4252/wjsc.v11.i12.1084. View

20.

Richards M, Tan S, Tan J, Chan W, Bongso A . The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells. 2003; 22(1):51-64. DOI: 10.1634/stemcells.22-1-51. View