Long-term expansion and differentiation of adult murine epidermal stem cells in 3D organoid cultures

被引：76

作者：

Boonekamp, Kim E. ^{[1
,2
,3
]}

Kretzschmar, Kai ^{[1
,2
,3
]}

Wiener, Dominique J. ^{[2
,3
,4
,5
,6
]}

Asra, Priyanca ^{[1
,2
,3
]}

Derakhshan, Sepideh ^{[2
,3
,7
]}

Puschhof, Jens ^{[1
,2
,3
]}

Lopez-Iglesias, Carmen ^{[8
]}

Peters, Peter J. ^{[8
]}

Basak, Onur ^{[2
,3
,9
]}

Clevers, Hans ^{[1
,2
,3
,7
]}

机构：

[1] Hubrecht Inst, Oncode Inst, NL-3584 CT Utrecht, Netherlands

[2] Royal Netherlands Acad Arts & Sci, Dev Biol & Stem Cell Res, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[4] Univ Bern, Inst Anim Pathol, Vetsuisse Fac, CH-3012 Bern, Switzerland

[5] Bern Univ Hosp, Inselspital, Dermfocus, Vetsuisse Fac, CH-3008 Bern, Switzerland

[6] Texas A&M Univ, Dept Vet Pathobiol, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA

[7] Princess Maxima Ctr Pediat Oncol, NL-3584 CS Utrecht, Netherlands

[8] Maastricht Univ, Maastricht Multimodal Mol Imaging Inst, NL-6229 ER Maastricht, Netherlands

[9] Univ Utrecht, Brain Ctr, Univ Med Ctr Utrecht, Dept Translat Neurosci, NL-3584 CG Utrecht, Netherlands

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2019年 / 116卷 / 29期

基金：

瑞士国家科学基金会;

关键词：

mammalian epidermis; organoids; adult stem cells; interfollicular epidermis; HAIR FOLLICLE; SKIN; KERATINOCYTES; PROLIFERATION; DESMOPLAKIN; GROWTH; CLASSIFICATION; ORGANIZATION; HOMEOSTASIS; PLASTICITY;

D O I：

10.1073/pnas.1715272116

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：

Mammalian epidermal stem cells maintain homeostasis of the skin epidermis and contribute to its regeneration throughout adult life. While 2D mouse epidermal stem cell cultures have been established decades ago, a long-term, feeder cell- and serum-free culture system recapitulating murine epidermal architecture has not been available. Here we describe an epidermal organoid culture system that allows long-term, genetically stable expansion of adult epidermal stem cells. Our epidermal expansion media combines atypically high calcium concentrations, activation of cAMP, FGF, and R-spondin signaling with inhibition of bone morphogenetic protein (BMP) signaling. Organoids are established robustly from adult mouse skin and expand over at least 6 mo, while maintaining the basal-apical organization of the mouse interfollicular epidermis. The system represents a powerful tool to study epidermal homeostasis and disease in vitro.

引用

页码：14630 / 14638

页数：9

共 58 条

[1] Identification of stem cells in small intestine and colon by marker gene Lgr5 [J].