Organ-Level Quorum Sensing Directs Regeneration in Hair Stem Cell Populations

被引：191

作者：

Chen, Chih-Chiang ^{[1
,2
,3
,4
]}

Wang, Lei ^{[5
]}

Plikus, Maksim V. ^{[6
,7
,8
]}

Jiang, Ting Xin ^{[1
]}

Murray, Philip J. ^{[9
]}

Ramos, Raul ^{[6
,7
,8
]}

Guerrero-Juarez, Christian F. ^{[6
,7
,8
]}

Hughes, Michael W. ^{[10
,11
]}

Lee, Oscar K. ^{[12
,13
]}

Shi, Songtao ^{[14
]}

Widelitz, Randall B. ^{[1
]}

Lander, Arthur D. ^{[6
,8
,15
]}

Chuong, Cheng Ming ^{[1
,3
,4
,16
]}

机构：

[1] Univ So Calif, Dept Pathol, Los Angeles, CA 90033 USA

[2] Taipei Vet Gen Hosp, Dept Dermatol, Taipei 112, Taiwan

[3] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan

[4] Natl Yang Ming Univ, Dept Dermatol, Taipei 112, Taiwan

[5] Fourth Mil Med Univ, Sch Stomatol, State Key Lab Mil Stomatol, Dept Oral & Maxillofacial Surg, Xian 710032, Shaanxi, Peoples R China

[6] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA

[7] Univ Calif Irvine, Sue & Bill Gross Stem Cell Res Ctr, Irvine, CA 92697 USA

[8] Univ Calif Irvine, Ctr Complex Biol Syst, Irvine, CA 92697 USA

[9] Univ Dundee, Div Math, Dundee DD1 4HN, Scotland

[10] Natl Cheng Kung Univ, Int Lab Wound Repair & Regenerat, Tainan 701, Taiwan

[11] Natl Cheng Kung Univ, Inst Clin Med, Tainan 701, Taiwan

[12] Natl Yang Ming Univ, Taipei Vet Gen Hosp, Taipei & Ctr Stem Cell Res, Dept Orthopaed & Traumatol, Taipei 112, Taiwan

[13] Vet Gen Hosp, Taipei 112, Taiwan

[14] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA

[15] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA

[16] Natl Taiwan Univ, Res Ctr Dev Biol & Regenerat Med, Taipei 10617, Taiwan

来源：

CELL | 2015年 / 161卷 / 02期

基金：

中国国家自然科学基金; 美国国家科学基金会;

关键词：

MORPHOGEN GRADIENT; SKIN; ACTIVATION; FOLLICLE; GROWTH; NICHE; ESTABLISHMENT; MACROPHAGES; CHEMOKINES; BACTERIA;

D O I：

10.1016/j.cell.2015.02.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Coordinated organ behavior is crucial for an effective response to environmental stimuli. By studying regeneration of hair follicles in response to patterned hair plucking, we demonstrate that organ-level quorum sensing allows coordinated responses to skin injury. Plucking hair at different densities leads to a regeneration of up to five times more neighboring, unplucked resting hairs, indicating activation of a collective decision-making process. Through data modeling, the range of the quorum signal was estimated to be on the order of 1 mm, greater than expected for a diffusible molecular cue. Molecular and genetic analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs leads to recruitment of TNF-alpha-secreting macrophages, which accumulate and signal to both plucked and unplucked follicles. By coupling immune response with regeneration, this mechanism allows skin to respond predictively to distress, disregarding mild injury, while meeting stronger injury with full-scale cooperative activation of stem cells.

引用

页码：277 / 290

页数：14

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