PDGFRα marks distinct perivascular populations with different osteogenic potential within adipose tissue

Yiyun Wang, Jiajia Xu, Carolyn A. Meyers, Yongxing Gao, Ye Tian, Kristen Broderick, Bruno Peault, Aaron W. James

Research output: Contribution to journalArticle

Abstract

The perivascular niche within adipose tissue is known to house multipotent cells, including osteoblast precursors. However, the identity of perivascular subpopulations that may mineralize or ossify most readily is not known. Here, we utilize inducible PDGFRα (platelet-derived growth factor alpha) reporter animals to identify subpopulations of perivascular progenitor cells. Results showed that PDGFRα-expressing cells are present in four histologic niches within inguinal fat, including two perivascular locations. PDGFRα+ cells are most frequent within the tunica adventitia of arteries and veins, where PDGFRα+ cells populate the inner aspects of the adventitial layer. Although both PDGFRα+ and PDGFRα fractions are multipotent progenitor cells, adipose tissue-derived PDGFRα+ stromal cells proliferate faster and mineralize to a greater degree than their PDGFRα counterparts. Likewise, PDGFRα+ ectopic implants reconstitute the perivascular niche and ossify to a greater degree than PDGFRα cell fractions. Adventicytes can be further grouped into three distinct groups based on expression of PDGFRα and/or CD34. When further partitioned, adventicytes co-expressing PDGFRα and CD34 represented a cell fraction with the highest mineralization potential. Long-term tracing studies showed that PDGFRα-expressing adventicytes give rise to adipocytes, but not to other cells within the vessel wall under homeostatic conditions. However, upon bone morphogenetic protein 2 (BMP2)-induced ossicle formation, descendants of PDGFRα+ cells gave rise to osteoblasts, adipocytes, and “pericyte-like” cells within the ossicle. In sum, PDGFRα marks distinct perivascular osteoprogenitor cell subpopulations within adipose tissue. The identification of perivascular osteoprogenitors may contribute to our improved understanding of pathologic mineralization/ossification. Stem Cells 2019.

Original languageEnglish (US)
JournalStem Cells
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Platelet-Derived Growth Factor
Adipose Tissue
Population
Adventitia
Stem Cells
Osteoblasts
Adipocytes
Heterotopic Ossification
Bone Morphogenetic Protein 2
Pericytes
Groin
Stromal Cells
Veins

Keywords

  • adipose stem cell
  • adventicyte
  • adventitial cell
  • mesenchymal stem cell
  • pericyte
  • perivascular stem cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

PDGFRα marks distinct perivascular populations with different osteogenic potential within adipose tissue. / Wang, Yiyun; Xu, Jiajia; Meyers, Carolyn A.; Gao, Yongxing; Tian, Ye; Broderick, Kristen; Peault, Bruno; James, Aaron W.

In: Stem Cells, 01.01.2019.

Research output: Contribution to journalArticle

Wang, Yiyun ; Xu, Jiajia ; Meyers, Carolyn A. ; Gao, Yongxing ; Tian, Ye ; Broderick, Kristen ; Peault, Bruno ; James, Aaron W. / PDGFRα marks distinct perivascular populations with different osteogenic potential within adipose tissue. In: Stem Cells. 2019.
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AU - Wang, Yiyun

AU - Xu, Jiajia

AU - Meyers, Carolyn A.

AU - Gao, Yongxing

AU - Tian, Ye

AU - Broderick, Kristen

AU - Peault, Bruno

AU - James, Aaron W.

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AB - The perivascular niche within adipose tissue is known to house multipotent cells, including osteoblast precursors. However, the identity of perivascular subpopulations that may mineralize or ossify most readily is not known. Here, we utilize inducible PDGFRα (platelet-derived growth factor alpha) reporter animals to identify subpopulations of perivascular progenitor cells. Results showed that PDGFRα-expressing cells are present in four histologic niches within inguinal fat, including two perivascular locations. PDGFRα+ cells are most frequent within the tunica adventitia of arteries and veins, where PDGFRα+ cells populate the inner aspects of the adventitial layer. Although both PDGFRα+ and PDGFRα− fractions are multipotent progenitor cells, adipose tissue-derived PDGFRα+ stromal cells proliferate faster and mineralize to a greater degree than their PDGFRα− counterparts. Likewise, PDGFRα+ ectopic implants reconstitute the perivascular niche and ossify to a greater degree than PDGFRα− cell fractions. Adventicytes can be further grouped into three distinct groups based on expression of PDGFRα and/or CD34. When further partitioned, adventicytes co-expressing PDGFRα and CD34 represented a cell fraction with the highest mineralization potential. Long-term tracing studies showed that PDGFRα-expressing adventicytes give rise to adipocytes, but not to other cells within the vessel wall under homeostatic conditions. However, upon bone morphogenetic protein 2 (BMP2)-induced ossicle formation, descendants of PDGFRα+ cells gave rise to osteoblasts, adipocytes, and “pericyte-like” cells within the ossicle. In sum, PDGFRα marks distinct perivascular osteoprogenitor cell subpopulations within adipose tissue. The identification of perivascular osteoprogenitors may contribute to our improved understanding of pathologic mineralization/ossification. Stem Cells 2019.

KW - adipose stem cell

KW - adventicyte

KW - adventitial cell

KW - mesenchymal stem cell

KW - pericyte

KW - perivascular stem cell

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