Single-cell Transcriptome Analysis of Stem Cells from Human Exfoliated Deciduous Teeth Investigating Functional Heterogeneity in Immunomodulation

Overview

Journal Sci Rep

Specialty Science

Date 2024 Dec 29

PMID 39732760

Authors

Yin Li

GuangYuan Song

Yu Jiang

Haitao Zhao

Yizhun Zhu

Shanshan Song

Lulu Wang

Xueying Wu

Affiliations

Soon will be listed here.

Abstract

Mesenchymal stem cells (MSCs) have been widely used in the treatment of various inflammatory diseases. The inadequate understanding of MSCs and their heterogeneity can impact the immune environment, which may be the cause of the good outcomes of MSCs-based therapy that cannot always be achieved. Recently, stem cells from human exfoliated deciduous teeth (SHED) showed great potential in inflammatory and autoimmune diseases due to their immature properties compared with MSCs. In our study, single-cell RNA sequencing (scRNA-seq) revealed that SHED in a low differentiation state (S7) exhibited the powerful ability to recruit multiple immune cells. In contrast, SHED in a relatively high differentiation state (S1) may hold a solid ability to secret many factors with paracrine signaling capacity. The analysis result shows that SHED has more robust immunomodulatory properties than human bone marrow-derived mesenchymal stem cells (hBMSCs) or human umbilical cord-derived mesenchymal stem cells (hUCMSCs). When co-cultured with PBMCs, SHED can enhance the proliferation of Treg and down-regulate TNF-α in vitro. SHED may have some advantages in the treatment of inflammatory and autoimmune diseases.

References

Argmann C, Hou R, Ungaro R, Irizar H, Al-Taie Z, Huang R . Biopsy and blood-based molecular biomarker of inflammation in IBD. Gut. 2022; 72(7):1271-1287. PMC: 10014487. DOI: 10.1136/gutjnl-2021-326451. View

Zhang Q, Yu J, Chen Q, Yan H, Du H, Luo W . Regulation of pathophysiological and tissue regenerative functions of MSCs mediated via the WNT signaling pathway (Review). Mol Med Rep. 2021; 24(3). PMC: 8299209. DOI: 10.3892/mmr.2021.12287. View

Cao D, Chan R, Ng E, Gemzell-Danielsson K, Yeung W . Single-cell RNA sequencing of cultured human endometrial CD140bCD146 perivascular cells highlights the importance of in vivo microenvironment. Stem Cell Res Ther. 2021; 12(1):306. PMC: 8164319. DOI: 10.1186/s13287-021-02354-1. View

Zha K, Yang Y, Tian G, Sun Z, Yang Z, Li X . Nerve growth factor (NGF) and NGF receptors in mesenchymal stem/stromal cells: Impact on potential therapies. Stem Cells Transl Med. 2021; 10(7):1008-1020. PMC: 8235142. DOI: 10.1002/sctm.20-0290. View

Pavlidis P, Tsakmaki A, Pantazi E, Li K, Cozzetto D, Digby-Bell J . Interleukin-22 regulates neutrophil recruitment in ulcerative colitis and is associated with resistance to ustekinumab therapy. Nat Commun. 2022; 13(1):5820. PMC: 9530232. DOI: 10.1038/s41467-022-33331-8. View

Medrano-Trochez C, Chatterjee P, Pradhan P, Stevens H, Ogle M, Botchwey E . Single-cell RNA-seq of out-of-thaw mesenchymal stromal cells shows tissue-of-origin differences and inter-donor cell-cycle variations. Stem Cell Res Ther. 2021; 12(1):565. PMC: 8567133. DOI: 10.1186/s13287-021-02627-9. View

Kim J, Park S, Kim W, Song S, Sung J . Functional regulation of adipose-derived stem cells by PDGF-D. Stem Cells. 2014; 33(2):542-56. DOI: 10.1002/stem.1865. View

Xiong X, Kuang H, Ansari S, Liu T, Gong J, Wang S . Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis. Mol Cell. 2019; 75(3):644-660.e5. PMC: 7262680. DOI: 10.1016/j.molcel.2019.07.028. View

Nourshargh S, Alon R . Leukocyte migration into inflamed tissues. Immunity. 2014; 41(5):694-707. DOI: 10.1016/j.immuni.2014.10.008. View

10.

Szemes M, Greenhough A, Melegh Z, Malik S, Yuksel A, Catchpoole D . Wnt Signalling Drives Context-Dependent Differentiation or Proliferation in Neuroblastoma. Neoplasia. 2018; 20(4):335-350. PMC: 5909736. DOI: 10.1016/j.neo.2018.01.009. View

11.

Yang N, Liu X, Chen X, Yu S, Yang W, Liu Y . Stem cells from exfoliated deciduous teeth transplantation ameliorates Sjögren's syndrome by secreting soluble PD-L1. J Leukoc Biol. 2021; 111(5):1043-1055. DOI: 10.1002/JLB.6MA0921-752RR. View

12.

Sato K, Tsuyuzaki K, Shimizu K, Nikaido I . CellFishing.jl: an ultrafast and scalable cell search method for single-cell RNA sequencing. Genome Biol. 2019; 20(1):31. PMC: 6371477. DOI: 10.1186/s13059-019-1639-x. View

13.

Ma L, Huang Z, Wu D, Kou X, Mao X, Shi S . CD146 controls the quality of clinical grade mesenchymal stem cells from human dental pulp. Stem Cell Res Ther. 2021; 12(1):488. PMC: 8404346. DOI: 10.1186/s13287-021-02559-4. View

14.

Zhu R, Yan T, Feng Y, Liu Y, Cao H, Peng G . Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms. Cell Res. 2021; 31(12):1244-1262. PMC: 8546390. DOI: 10.1038/s41422-021-00573-y. View

15.

Wang Z, Chai C, Wang R, Feng Y, Huang L, Zhang Y . Single-cell transcriptome atlas of human mesenchymal stem cells exploring cellular heterogeneity. Clin Transl Med. 2021; 11(12):e650. PMC: 8715893. DOI: 10.1002/ctm2.650. View

16.

Yasui T, Mabuchi Y, Toriumi H, Ebine T, Niibe K, Houlihan D . Purified Human Dental Pulp Stem Cells Promote Osteogenic Regeneration. J Dent Res. 2015; 95(2):206-14. DOI: 10.1177/0022034515610748. View

17.

Liu F, Qiu H, Xue M, Zhang S, Zhang X, Xu J . MSC-secreted TGF-β regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway. Stem Cell Res Ther. 2019; 10(1):345. PMC: 6878630. DOI: 10.1186/s13287-019-1447-y. View

18.

Freeman B, Jung J, Ogle B . Single-Cell RNA-Seq of Bone Marrow-Derived Mesenchymal Stem Cells Reveals Unique Profiles of Lineage Priming. PLoS One. 2015; 10(9):e0136199. PMC: 4564185. DOI: 10.1371/journal.pone.0136199. View

19.

Elsafadi M, Manikandan M, Dawud R, Alajez N, Hamam R, Alfayez M . Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization. Cell Death Dis. 2016; 7(8):e2321. PMC: 5108308. DOI: 10.1038/cddis.2016.196. View

20.

Qiu X, Mao Q, Tang Y, Wang L, Chawla R, Pliner H . Reversed graph embedding resolves complex single-cell trajectories. Nat Methods. 2017; 14(10):979-982. PMC: 5764547. DOI: 10.1038/nmeth.4402. View