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CX3CL1/CX3CR1-signalling in the CD9/S100β/SOX2-positive adult pituitary stem/progenitor cells modulates differentiation into endothelial cells

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Abstract

Approximately 8% of CD9-, S100β- and SOX2-triple positive (CD9/S100β/SOX2-positive) stem/progenitor cells in the anterior lobe of the rat pituitary gland have previously been shown to differentiate into endothelial cells in vitro, suggesting that they play a role in vascularisation as tissue-resident vascular precursor cells. In the present study, we focused on chemokine ligands to further characterise the CD9/S100β/SOX2-positive cells and found that they distinctively express CX3C chemokine ligand 1 (Cx3cl1). Immunohistochemical analysis of the anterior lobe showed that CX3CL1-positive cells comprised 7.8% in CD9-positive cells. By cultivation of the CD9-positive cells on laminin-coated plates, we observed that the expression levels of Cx3cl1 decreased, while those of Sox18, an endothelial cell-progenitor marker, and Cx3cr1, a CX3CL1 receptor, increased. Furthermore, in a rat model of prolactinoma, the most common pituitary tumour, which is accompanied by frequent neo-vasculogenesis in the anterior lobe, we have confirmed a decrease in Cx3cl1 expression and an increase in Cx3cr1 expression, as well as a prominent increase in Sox18 expression. These findings suggest that CX3CL1/CX3CR1 signalling in CD9/S100β/SOX2-positive cells plays an important role in resupplying endothelial cells for vascular remodelling in the anterior lobe.

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Abbreviations

ALK:

Type I receptors activin receptor- like kinase

BMP:

Bone morphogenic protein

XCR1:

C chemokine receptors

CCRs:

CC chemokine receptors

CD9/S100β/SOX2-positive:

CD9-, S100β- and SOX2-triple positive

CXCL:

CXC chemokine ligand

CX3CL1:

CX3C chemokine ligand 1

CX3CR1:

CX3CL1 receptor

DES:

Diethylstilboestrol

DIG:

Digoxigenin

FBS:

Foetal bovine serum

HE:

Haematoxylin–eosin

ID:

Inhibitor of differentiation

PB:

Phosphate buffer

P0:

Postnatal day 0

SOX2:

Sex-determining region Y-box 2

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Acknowledgements

We are grateful to Dr. Tom Kouki for his excellent technical assistance with TEM. We thank “Joint Usage/Research Center for Endocrine/Metabolism, Institute for Molecular and Cellular Regulation, Gunma University” (www.imcr.gunma-u.ac.jp/activity/activity3) as the source of the antibodies. We are grateful to Miss Kozue Tateno for her excellent technical assistance. We would like to thank Editage (www.editage.jp) for English language editing.

Funding

This work was supported by JSPS KAKENHI (Grant Nos. 16K08475 to K.H., 21380184 to Y.K. and 24580435 to T.K.), by a MEXT-supported Program for the Strategic Research Foundation at Private Universities (2014–2018) and by the Meiji University International Institute for BioResource Research (MUIIR).

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Authors and Affiliations

  1. Laboratory of Anatomy and Cell Biology, Department of Health Sciences, Kyorin University, 5-4-1 Shimorenjaku, Mitaka, Tokyo, 181-8612, Japan

    Kotaro Horiguchi, Rumi Hasegawa, Shu Takigami & Shunji Ohsako

  2. Institute for Endocrinology, Meiji University, 1-1-1 Higashi-mita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan

    Kotaro Horiguchi, Saishu Yoshida, Takako Kato & Yukio Kato

  3. Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan

    Ken Fujiwara & Takashi Yashiro

  4. Department of Biochemistry, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan

    Saishu Yoshida

  5. Department of Biomolecular Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba, 274-8510, Japan

    Takehiro Tsukada

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  1. Kotaro Horiguchi
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  2. Ken Fujiwara
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Correspondence to Kotaro Horiguchi or Yukio Kato.

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The current study was approved by the Committee on Animal Experiments of the School of Agriculture, Meiji University, and Kyorin University based on the NIH Guidelines for the Care and Use of Laboratory Animals. This article does not contain any studies with human participants.

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Horiguchi, K., Fujiwara, K., Yoshida, S. et al. CX3CL1/CX3CR1-signalling in the CD9/S100β/SOX2-positive adult pituitary stem/progenitor cells modulates differentiation into endothelial cells. Histochem Cell Biol 153, 385–396 (2020). https://doi.org/10.1007/s00418-020-01862-0

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