Identification and isolation of a dermal lineage with intrinsic fibrogenic potential

被引：520

作者：

Rinkevich, Yuval ^{[1
,2
]}

Walmsley, Graham G. ^{[1
,2
,3
]}

Hu, Michael S. ^{[1
,2
,3
]}

Maan, Zeshaan N. ^{[3
]}

Newman, Aaron M. ^{[1
,2
]}

Drukker, Micha ^{[1
,2
]}

Januszyk, Michael ^{[3
]}

Krampitz, Geoffrey W. ^{[1
,2
]}

Gurtner, Geoffrey C. ^{[3
]}

Lorenz, H. Peter ^{[3
]}

Weissman, Irving L. ^{[1
,2
,4
]}

Longaker, Michael T. ^{[1
,2
,3
]}

机构：

[1] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Dept Pathol, Stanford, CA 94305 USA

[2] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Dept Dev Biol, Stanford, CA 94305 USA

[3] Stanford Univ, Hagey Lab Pediat Regenerat Med, Sch Med, Dept Surg Plast & Reconstruct Surg, Stanford, CA 94305 USA

[4] Stanford Univ, Ludwig Ctr Canc Stem Cell Biol & Med, Sch Med, Stanford, CA 94305 USA

来源：

SCIENCE | 2015年 / 348卷 / 6232期

关键词：

STROMAL CELLS; CIRCULATING FIBROCYTES; BREAST FIBROBLASTS; PROTEIN-ALPHA; HOST-CELLS; SKIN; MYOFIBROBLASTS; EXPRESSION; FIBROSIS; CANCER;

D O I：

10.1126/science.aaa2151

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate that a single fibroblast lineage is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation. Lineage-specific cell ablation leads to diminished connective tissue deposition in wounds and reduces melanoma growth. Using flow cytometry, we identify CD26/DPP4 as a surface marker that allows isolation of this lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. Identification and isolation of these lineages hold promise for translational medicine aimed at in vivo modulation of fibrogenic behavior.

引用

页数：15

共 43 条

[21] INTRA-TUMOR HOST-CELLS OF TRANSPLANTED RAT NEOPLASMS OF DIFFERENT IMMUNOGENICITY [J].