Skip to main content

Advertisement

SpringerLink
Log in

Notch1 down-regulation in lineage-restricted niches is involved in the development of mouse eccrine sweat glands

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

Eccrine sweat gland (SG) restrictedly exists in mouse foot pads indicating that mouse plantar dermis (PD) contains the SG lineage-restricted niches. However, it is still unclear how these niches can affect stem cell fate towards SG. In this study, we tried to find the key cues by which stem cells sense and interact with the SG lineage-specific niches both in vivo and in vitro. Firstly, we used transcriptomics RNA sequencing analysis to screen differentially expressed genes between SG cells and epidermal stem cells (ES), and used proteomic analysis to screen differentially expressed proteins between PD and dorsal dermis (DD). Notch1 was found differentially expressed in both gene and protein levels, and was closely related to SG morphogenesis based on Gene Ontology (GO) enrichment analysis. Secondly, the spatial-temporal changes of Notch1 during embryonic and post-natal development of SG were detected. Thirdly, mouse mesenchymal stem cells (MSCs) were introduced into SG-like cells in vitro in order to further verify the possible roles of Notch1. Results revealed that Notch1 was continuously down-regulated along with the process of SG morphogenesis in vivo, and also along with the process that MSCs differentiated into SG-like cells in vitro. Hence, we suggest that Notch1 possibly acts as with roles of “gatekeeper” during SG development and regulates the interactions between stem cells and the SG lineage-specific niches. This study might help for understanding mechanisms of embryonic SG organogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

All the data and materials in this study are available from the corresponding author upon reasonable request.

Abbreviations

DD:

dorsal dermis.

E:

embryonic day.

ES:

epidermal stem cell.

GO:

Gene Ontology.

iTRAQ:

isobaric tags for relative and absolute quantification.

K14:

keratin 14.

K8:

keratin 8.

MSCs:

mesenchymal stem cells.

P:

postpartum day.

PD:

plantar dermis.

RT-qPCR:

real-time quantitative polymerase chain reaction.

SG:

sweat gland.

References

  • Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776

    Article  CAS  Google Scholar 

  • Bello AB, Park H, Lee SH (2018) Current approaches in biomaterial-based hematopoietic stem cell niches. Acta Biomater 72:1–15

    Article  CAS  Google Scholar 

  • Biedermann T, Pontiggia L, Böttcher-Haberzeth S, Tharakan S, Braziulis E, Schiestl C, Meuli M, Reichmann E (2010) Human eccrine sweat gland cells can reconstitute a stratified epidermis.J Invest Dermatol 130,1996–2009

  • Centonze A, Lin S, Tika E, Sifrim A, Fioramonti M, Malfait M, Song Y, Wuidart A, Van Herck J, Dannau A et al (2020) Heterotypic cell-cell communication regulates glandular stem cell multipotency. Nature 584:608–613

    Article  CAS  Google Scholar 

  • Chee MK, Jo SK, Sohn KC, Kim CD, Lee JH, Lee YH (2017) Effects of Brn2 overexpression on eccrine sweat gland development in the mouse paw. Biochem Biophys Res Commun 490:901–905

    Article  CAS  Google Scholar 

  • Csaszar E, Kirouac DC, Yu M, Wang W, Qiao W, Cooke MP, Boitano AE, Ito C, Zandstra PW (2012) Rapid expansion of human hematopoietic stem cells by automated control of inhibitory feedback signaling. Cell Stem Cell 10:218–229

    Article  CAS  Google Scholar 

  • Ferraris C, Chevalier G, Favier B, Jahoda CA, Dhouailly D (2000) Adult corneal epithelium basal cells possess the capacity to activate epidermal, pilosebaceous and sweat gland genetic programs in response to embryonic dermal stimuli. Development 127:5487–5495

    Article  CAS  Google Scholar 

  • Fu NY, Nolan E, Lindeman GJ, Visvader JE (2020) Stem Cells and the Differentiation Hierarchy in Mammary Gland Development. Physiol Rev 100:489–523

    Article  CAS  Google Scholar 

  • He T, Bai X, Jing J, Liu Y, Wang H, Zhang W, Li X, Li Y, Wang L, Xie S et al (2020) Notch signal deficiency alleviates hypertrophic scar formation after wound healing through the inhibition of inflammation. Arch Biochem Biophys 682:108286

    Article  CAS  Google Scholar 

  • Hu T, Xu Y, Yao B, Fu X, Huang S (2019) Developing a Novel and Convenient Model for Investigating Sweat Gland Morphogenesis from Epidermal Stem Cells.Stem Cells Int 2019,4254759

  • Li H, Chen L, Zhang M, Zhang B (2017) Foxa1 gene and protein in developing rat eccrine sweat glands. J Mol Histol 48:1–7

    Article  Google Scholar 

  • Lilja AM, Rodilla V, Huyghe M, Hannezo E, Landragin C, Renaud O, Leroy O, Rulands S, Simons BD, Fre S (2018) Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland. Nat Cell Biol 20:677–687

    Article  CAS  Google Scholar 

  • Liu F, Wang S (2014) Molecular cues for development and regeneration of salivary glands. Histol Histopathol 29:305–312

    CAS  PubMed  Google Scholar 

  • Liu Y, Li J, Yao B, Wang Y, Wang R, Yang S, Li Z, Zhang Y, Huang S, Fu X (2021) The stiffness of hydrogel-based bioink impacts mesenchymal stem cells differentiation toward sweat glands in 3D-bioprinted matrix. Mater Sci Eng C Mater Biol Appl 118:111387

    Article  CAS  Google Scholar 

  • Lloyd-Lewis B, Mourikis P, Fre S (2019) Notch signalling: sensor and instructor of the microenvironment to coordinate cell fate and organ morphogenesis. Curr Opin Cell Biol 61:16–23

    Article  CAS  Google Scholar 

  • Lu C, Fuchs E (2014) Sweat gland progenitors in development, homeostasis, and wound repair.Cold Spring Harb Perspect Med 4

  • Lu CP, Polak L, Keyes BE, Fuchs E (2016) Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision.Science 354

  • Lu CP, Polak L, Rocha AS, Pasolli HA, Chen SC, Sharma N, Blanpain C, Fuchs E (2012) Identification of stem cell populations in sweat glands and ducts reveals roles in homeostasis and wound repair. Cell 150:136–150

    Article  CAS  Google Scholar 

  • Lutolf MP, Blau HM (2009) Artificial stem cell niches. Adv Mater 21:3255–3268

    Article  CAS  Google Scholar 

  • Morrison SJ, Spradling AC (2008) Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132:598–611

    Article  CAS  Google Scholar 

  • Nabhan AN, Brownfield DG, Harbury PB, Krasnow MA, Desai TJ (2018) Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells. Science 359:1118–1123

    Article  CAS  Google Scholar 

  • Navarro Negredo P, Yeo RW, Brunet A (2020) Aging and Rejuvenation of Neural Stem Cells and Their Niches. Cell Stem Cell 27:202–223

    Article  CAS  Google Scholar 

  • Pinho S, Frenette PS (2019) Haematopoietic stem cell activity and interactions with the niche. Nat Rev Mol Cell Biol 20:303–320

    Article  CAS  Google Scholar 

  • Rishikaysh P, Dev K, Diaz D, Qureshi WM, Filip S, Mokry J (2014) Signaling involved in hair follicle morphogenesis and development. Int J Mol Sci 15:1647–1670

    Article  CAS  Google Scholar 

  • Scadden DT (2006) The stem-cell niche as an entity of action. Nature 441:1075–1079

    Article  CAS  Google Scholar 

  • Scadden DT (2014) Nice neighborhood: emerging concepts of the stem cell niche.Cell 157,41–50

  • Vining KH, Mooney DJ (2017) Mechanical forces direct stem cell behaviour in development and regeneration. Nat Rev Mol Cell Biol 18:728–742

    Article  CAS  Google Scholar 

  • Wang R, Wang Y, Yao B, Hu T, Li Z, Liu Y, Cui X, Cheng L, Song W, Huang S et al (2019) Redirecting differentiation of mammary progenitor cells by 3D bioprinted sweat gland microenvironment. Burns Trauma 7:29

    Article  Google Scholar 

  • Wang Y, Wang R, Yao B, Hu T, Li Z, Liu Y, Cui X, Cheng L, Song W, Huang S et al (2020) TNF-α suppresses sweat gland differentiation of MSCs by reducing FTO-mediated m(6)A-demethylation of Nanog mRNA. Sci China Life Sci 63:80–91

    Article  CAS  Google Scholar 

  • Xie J, Yao B, Han Y, Shang T, Gao D, Yang S, Ma K, Huang S, Fu X (2015) Cytokeratin Expression at Different Stages in Sweat Gland Development of C57BL/6J Mice. Int J Low Extrem Wounds 14:365–371

    Article  CAS  Google Scholar 

  • Yao B, Wang R, Wang Y, Zhang Y, Hu T, Song W, Li Z, Huang S, Fu X (2020) Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration.Sci Adv 6,eaaz1094

  • Yao B, Xie J, Liu N, Yan T, Li Z, Liu Y, Huang S, Fu X (2016) Identification of a new sweat gland progenitor population in mice and the role of their niche in tissue development. Biochem Biophys Res Commun 479:670–675

    Article  CAS  Google Scholar 

  • Yuzhen W, Bin Y, Xianlan D, Jianjun L, Wei S, Enhe J, Zhao L, Xingyu Y, Yi K, Yijie Z et al (2022) Notch1 down-regulation in lineage-restricted niches of mouse eccrine sweat glands. Research Square

Download references

Acknowledgements

We are grateful for the kind assistances of all the members in our lab. This manuscript was submitted as a pre-print in the link https://www.researchsquare.com/article/rs-596907/v1 (Yuzhen et al., 2022).

Funding

This study was supported by the National Nature Science Foundation of China (82002056, 81830064, 81721092, 32000969), China Postdoctoral Science Foundation (2020M673672), the Beijing Natural Science Foundation (7204306), Key Support Program for Growth Factor Research (SZYZ-TR-03), Chinese PLA General Hospital for Military Medical Innovation Research Project (CX19026), the CAMS Innovation Fund for Medical Sciences (CIFMS, 2019-I2M-5-059) and the Military Medical Research and Development Projects (AWS17J005).

Author information

Authors and Affiliations

  1. Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department, Chinese PLA General Hospital, 28 Fu Xing Road, 100048, Beijing, P. R. China

    Yuzhen Wang, Bin Yao, Xianlan Duan, Jianjun Li, Wei Song,  Enhejirigala, Zhao Li, Xingyu Yuan, Yi Kong, Yijie Zhang, Xiaobing Fu & Sha Huang

  2. PLA Key Laboratory of Tissue Repair and Regenerative Medicine, Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Chinese PLA General Hospital and PLA Medical College, 28 Fu Xing Road, 100048, Beijing, P.R. China

    Yuzhen Wang, Bin Yao, Xianlan Duan, Jianjun Li,  Enhejirigala, Xingyu Yuan, Yi Kong, Yijie Zhang & Xiaobing Fu

  3. Department of Burn and Plastic Surgery, Air Force Hospital of Chinese PLA Central Theater Command, 589 Yunzhong Road, Pingcheng District, 037006, Datong, Shanxi, P. R. China

    Yuzhen Wang

  4. Academy of Medical Engineering and Translational Medicine, Tianjin University, 300072, Tianjin, P. R. China

    Bin Yao

  5. School of Medicine, Nankai University, 94 Wei Jing Road, 300071, Tianjin, P.R. China

    Xianlan Duan & Xingyu Yuan

  6. Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, 28 Fu Xing Road, 100853, Beijing, P.R. China

    Jianjun Li

  7. Institute of Basic Medical Research, Inner Mongolia Medical University, Hohhot, Inner Mongolia, P.R. China

    Enhejirigala

  8. College of Graduate, Tianjin Medical University, 22 Qi Xiang Tai Road, 300050, Tianjin, P.R. China

    Enhejirigala

  9. Department of Clinical Laboratory, the First Medical Center, Chinese PLA General Hospital, 28 Fu Xing Road, 100853, Beijing, P.R. China

    Yi Kong

Authors
  1. Yuzhen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bin Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xianlan Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jianjun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Enhejirigala
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xingyu Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yi Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yijie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xiaobing Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sha Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Yuzhen Wang proposed the detailed plan of this research, carried out most of the experiments and wrote the manuscript. Bin Yao provided step-by-step instructions and performed RNA sequencing analysis and proteomic analysis. Xianlan Duan, Jianjun Li, and Wei Song harvested and cultured SG cells and ES. Enhejirigala, Zhao Li, Xingyu Yuan, Yi Kong, and Yijie Zhang provided help in making figures and analyzing data. Xiaobing Fu and Sha Huang provided the most funding fees, supervised the whole process of research and edited the manuscript.

Corresponding authors

Correspondence to Xiaobing Fu or Sha Huang.

Ethics declarations

Ethics approval and consent to participate

All animal procedures were approved (approval number SCXK(BJ)2019-0001) and supervised by Institutional Animal Care and USE Committee of Chinese PLA General Hospital (Beijing, China).

Consent for publication

All authors have provided their consent to publish.

Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Yao, B., Duan, X. et al. Notch1 down-regulation in lineage-restricted niches is involved in the development of mouse eccrine sweat glands. J Mol Histol 53, 857–867 (2022). https://doi.org/10.1007/s10735-022-10098-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-022-10098-2

Keywords

Search

Navigation