[논문]Distinct fibroblast subsets regulate lacteal integrity through YAP/TAZ-induced VEGF-C in intestinal villi

Hong, Seon Pyo; Yang, Myung Jin; Cho, Hyunsoo; Park, Intae; Bae, Hosung; Choe, Kibaek; Suh, Sang Heon; Adams, Ralf H.; Alitalo, Kari; Lim, Daesik; Koh, Gou Young

doi:10.1038/s41467-020-17886-y

[해외논문] Distinct fibroblast subsets regulate lacteal integrity through YAP/TAZ-induced VEGF-C in intestinal villi 원문보기

Nature communications, v.11 no.1 = v.11, 2020년, pp.4102 -

Hong, Seon Pyo (Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, 34141 Republic of Korea) , Yang, Myung Jin (Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141 Republic of Korea) , Cho, Hyunsoo (Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, 34141 Republic of Korea) , Park, Intae (Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, 34141 Republic of Korea) , Bae, Hosung (Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, 34141 Republic of Korea) , Choe, Kibaek (Graduate School of Nanoscience and Technology, KAIST, Daejeon, 34141 Republic of Korea) , Suh, Sang Heon (Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, 34141 Republic of Korea) , Adams, Ralf H. (Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, and University of Mü) , Alitalo, Kari (nster, D-48149 Mü) , Lim, Daesik (nster, Germany) , Koh, Gou Young (Translational Cancer Biology Program and Wihuri Research Institute, Biomedicum Helsinki, University of Hel)

Abstract ▼ AI-Helper

Emerging evidence suggests that intestinal stromal cells (IntSCs) play essential roles in maintaining intestinal homeostasis. However, the extent of heterogeneity within the villi stromal compartment and how IntSCs regulate the structure and function of specialized intestinal lymphatic capillary called lacteal remain elusive. Here we show that selective hyperactivation or depletion of YAP/TAZ in PDGFRβ+ IntSCs leads to lacteal sprouting or regression with junctional disintegration and impaired dietary fat uptake. Indeed, mechanical or osmotic stress regulates IntSC secretion of VEGF-C mediated by YAP/TAZ. Single-cell RNA sequencing delineated novel subtypes of villi fibroblasts that upregulate Vegfc upon YAP/TAZ activation. These populations of fibroblasts were distributed in proximity to lacteal, suggesting that they constitute a peri-lacteal microenvironment. Our findings demonstrate the heterogeneity of IntSCs and reveal that distinct subsets of villi fibroblasts regulate lacteal integrity through YAP/TAZ-induced VEGF-C secretion, providing new insights into the dynamic regulatory mechanisms behind lymphangiogenesis and lymphatic remodeling.Intestinal stromal cells (IntSCs) play essential roles in maintaining intestinal homeostasis. Here the authors show that VEGF-C expression in specialized IntSCs is regulated by YAP/TAZ, and VEGF-C is responsible for maintaining lacteal integrity, thus influencing dietary fat drainage into lacteals.

참고문헌 (53)

1. Bernier-Latmani J Petrova TV Intestinal lymphatic vasculature: structure, mechanisms and functions. Nature reviews Gastroenterol. Hepatol. 2017 14 510 526
2. Aspelund A Robciuc MR Karaman S Makinen T Alitalo K Lymphatic system in cardiovascular medicine Circ. Res 2016 118 515 530 26846644

상세보기
3. Petrova TV Koh GY Organ-specific lymphatic vasculature: from development to pathophysiology J. Exp. Med. 2018 215 35 49 29242199

상세보기
4. Bernier-Latmani J DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport J. Clin. Investig. 2015 125 4572 4586 26529256
5. Nurmi H VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption EMBO Mol. Med. 2015 7 1418 1425 26459520

상세보기
6. Davis RB Kechele DO Blakeney ES Pawlak JB Caron KM Lymphatic deletion of calcitonin receptor-like receptor exacerbates intestinal inflammation JCI Insight 2017 2 e92465 28352669
7. Zhang F Lacteal junction zippering protects against diet-induced obesity Science 2018 361 599 603 30093598

상세보기
8. Hagerling, R. et al. Distinct roles of VE-cadherin for development and maintenance of specific lymph vessel beds. EMBO J. 37 , 10.15252/embj.201798271 (2018).
9. Stzepourginski I CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury Proc. Natl Acad. Sci. USA 2017 114 E506 E513 28074039

상세보기
10. Greicius G PDGFRalpha(+) pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells in vivo Proc. Natl Acad. Sci. USA 2018 115 E3173 E3181 29559533
11. Degirmenci B Valenta T Dimitrieva S Hausmann G Basler K GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells Nature 2018 558 449 453 29875413
12. Shoshkes-Carmel M Subepithelial telocytes are an important source of Wnts that supports intestinal crypts Nature 2018 557 242 246 29720649
13. Cao Z Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis Nat. Med 2016 22 154 162 26779814

상세보기
14. Tallquist MD Molkentin JD Redefining the identity of cardiac fibroblasts Nat. Rev. Cardiol. 2017 14 484 491 28436487

상세보기
15. Shook, B. A. et al. Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair. Science 10.1126/science.aar2971 (2018).
16. Di Carlo SE Peduto L The perivascular origin of pathological fibroblasts J. Clin. Investig. 2018 128 54 63 29293094
17. Hong AW Meng Z Guan KL The Hippo pathway in intestinal regeneration and disease. Nature reviews Gastroenterol. Hepatol. 2016 13 324 337
18. Totaro A Panciera T Piccolo S YAP/TAZ upstream signals and downstream responses Nat. Cell Biol. 2018 20 888 899 30050119

상세보기
19. Moya, I. M. & Halder, G. Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine. Nature reviews. Mol. Cell Biol. 10.1038/s41580-018-0086-y (2018).
20. Wang Y Deletion of yes-associated protein (YAP) specifically in cardiac and vascular smooth muscle cells reveals a crucial role for YAP in mouse cardiovascular development Circ. Res. 2014 114 957 965 24478334

상세보기
21. Kim J YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation J. Clin. Investig. 2017 127 3441 3461 28805663
22. Neto F YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development eLife 2018 7 e31037 29400648

상세보기
23. Kato K Pulmonary pericytes regulate lung morphogenesis Nat. Commun. 2018 9 2448 29934496

상세보기
24. Cho H YAP and TAZ negatively regulate Prox1 during developmental and pathologic lymphangiogenesis Circ. Res 2019 124 225 242 30582452

상세보기
25. Meng Z Moroishi T Guan KL Mechanisms of Hippo pathway regulation Genes Dev. 2016 30 1 17 26728553

상세보기
26. Halder G Dupont S Piccolo S Transduction of mechanical and cytoskeletal cues by YAP and TAZ Nat. Rev. Mol. cell Biol. 2012 13 591 600 22895435

상세보기
27. Aragona M A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors Cell 2013 154 1047 1059 23954413

상세보기
28. Wada K Itoga K Okano T Yonemura S Sasaki H Hippo pathway regulation by cell morphology and stress fibers Development 2011 138 3907 3914 21831922
29. Dupont S Role of YAP/TAZ in mechanotransduction Nature 2011 474 179 183 21654799

상세보기
30. Park DY Plastic roles of pericytes in the blood-retinal barrier Nat. Commun. 2017 8 15296 28508859

상세보기
31. Heallen T Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size Science 2011 332 458 461 21512031

상세보기
32. Kim M cAMP/PKA signalling reinforces the LATS-YAP pathway to fully suppress YAP in response to actin cytoskeletal changes EMBO J. 2013 32 1543 1555 23644383

상세보기
33. Baluk P Functionally specialized junctions between endothelial cells of lymphatic vessels J. Exp. Med. 2007 204 2349 2362 17846148

상세보기
34. Choe K Intravital imaging of intestinal lacteals unveils lipid drainage through contractility J. Clin. Investig. 2015 125 4042 4052 26436648
35. Suh, S. H. et al. Gut microbiota regulates lacteal integrity by inducing VEGF-C in intestinal villus macrophages. EMBO Rep. 10.15252/embr.201846927 (2019).
36. Choi D Laminar flow downregulates Notch activity to promote lymphatic sprouting. The J. Clin. Investig. 2017 127 1225 1240 28263185
37. Antila S Development and plasticity of meningeal lymphatic vessels J. Exp. Med. 2017 214 3645 3667 29141865

상세보기
38. Xin M Regulation of insulin-like growth factor signaling by Yap governs cardiomyocyte proliferation and embryonic heart size Sci. Signal 2011 4 ra70 22028467
39. Humphrey JD Dufresne ER Schwartz MA Mechanotransduction and extracellular matrix homeostasis Nat. Rev. Mol. cell Biol. 2014 15 802 812 25355505

상세보기
40. Lin KC Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation Nat. Cell Biol. 2017 19 996 1002 28752853

상세보기
41. Fu J Mechanical regulation of cell function with geometrically modulated elastomeric substrates Nat. Methods 2010 7 733 736 20676108

상세보기
42. Tropini C Transient osmotic perturbation causes long-term alteration to the gut microbiota Cell 2018 173 1742 1754 29906449

상세보기
43. Thomson CA Expression of the atypical chemokine receptor ACKR4 identifies a novel population of intestinal submucosal fibroblasts that preferentially expresses endothelial cell regulators J. Immunol. 2018 201 215 229 29760193

상세보기
44. Walton KD Villification in the mouse: Bmp signals control intestinal villus patterning Development 2016 143 427 436 26721501
45. Augustin, H. G. & Koh, G. Y. Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology. Science 10.1126/science.aal2379 (2017).
46. Vanlandewijck M A molecular atlas of cell types and zonation in the brain vasculature Nature 2018 554 475 480 29443965
47. Li Y Lui KO Zhou B Reassessing endothelial-to-mesenchymal transition in cardiovascular diseases Nat. Rev. Cardiol. 2018 15 445 456 29748594

상세보기
48. Owens BM Simmons A Intestinal stromal cells in mucosal immunity and homeostasis Mucosal Immunol. 2013 6 224 234 23235744

상세보기
49. Kinchen J Structural remodeling of the human colonic mesenchyme in inflammatory bowel disease Cell 2018 175 372 386 30270042

상세보기
50. Lorenz L Mechanosensing by beta1 integrin induces angiocrine signals for liver growth and survival Nature 2018 562 128 132 30258227
51. Ahn, J. H. et al. Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid. Nature 10.1038/s41586-019-1419-5 (2019).
52. Butler A Hoffman P Smibert P Papalexi E Satija R Integrating single-cell transcriptomic data across different conditions, technologies, and species Nat. Biotechnol. 2018 36 411 420 29608179

상세보기
53. Young MD Wakefield MJ Smyth GK Oshlack A Gene ontology analysis for RNA-seq: accounting for selection bias Genome Biol. 2010 11 R14 20132535

상세보기

LOADING...

활용도 분석정보

상세보기

다운로드

내보내기

활용도 Top5 논문

해당 논문의 주제분야에서 활용도가 높은 상위 5개 콘텐츠를 보여줍니다.
더보기 버튼을 클릭하시면 더 많은 관련자료를 살펴볼 수 있습니다.

원문 보기

AccessON 원문보기

원문 URL 링크

DOI : 10.1038/s41467-020-17886-y
ProQuest Medical Library : 저널
Nature Publishing : 저널
AccessON : 저널

*원문 PDF 파일 및 링크정보가 존재하지 않을 경우 KISTI DDS 시스템에서 제공하는 원문복사서비스를 사용할 수 있습니다.

오픈액세스(OA) 유형

GOLD

오픈액세스 학술지에 출판된 논문

저작권 관리 안내

내보내기 메뉴

내보내기 구분

파일저장
인쇄
메일전송

구성항목

기본정보
상세정보

관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관

저장형식

Text(ASCII format)
Excel format
RefWorks Direct Export
RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley

메일정보

받는사람 (필수): @
보내는사람 (선택): @
제목
내용: KISTI 검색결과 이메일 서비스

안내

총 건의 자료가 검색되었습니다.

다운받으실 자료의 인덱스를 입력하세요. (1-10,000)

검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다.

데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요)

다운로드 파일은 UTF-8 형태로 저장됩니다.
파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오.

Text(ASCII format)
Excel format

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

AI-Helper ※ AI-Helper는 을 사용합니다.

AI-Helper

안녕하세요, AI-Helper입니다. 좌측 "선택된 텍스트"에서 텍스트를 선택하여 요약, 번역, 용어설명을 실행하세요.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.

연합인증