Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart
Preprint posted on 2 July 2020 https://www.biorxiv.org/content/10.1101/2020.06.30.179952v1
Article now published in Development at http://dx.doi.org/10.1242/dev.194563
Categories: cell biology, developmental biology, immunology
Background
Macrophages are multifunctional innate immune cells that have key roles in immune responses, healing, development and homeostasis (1). During development, macrophages seed different tissues where the local microenvironment imprints a specific genetic signature, creating specialised tissue resident macrophages (2). The tissue resident macrophages are then essential for development of their associated tissue. During embryogenesis, this process occurs when macrophages become resident within the developing heart (3).
The heart is a highly vascularised organ with lymphatic capillaries and collecting lymphatic vessels making up the cardiac lymphatic vasculature (4). Recently, it has emerged that the lymphatic vasculature may represent an important therapeutic target, particularly in relation to lymphoangiogensis (5). Therefore, understanding how the cardiac lymphatics develop is an important step towards this.
Cahill et al investigated the importance and role of cardiac macrophages for lymphatic vessel growth within the developing heart.
Key findings
- Macrophages are associated with developing lymphatics
As heart development progresses, the number of macrophages present increase. Therefore, the authors imaged mid-stage mouse embryos (E12.5-E16.5) to investigate the localisation of macrophages with developing lymphatics. They found that macrophages are localised with the developing lymphatics and that removal of macrophages in mutants which lacked myeloid cells lymphatic development was stunted, with reduced length and numbers of junctions (figure 1).
Tissue resident macrophages can either be recruited from circulating monocytes or seeded by yolk-sac derived macrophages and self-renew. To address this, the authors stained with markers of these different ontogenies and found that the yolk-sac derived macrophages were those associated with developing lymphatics. The loss of these macrophages subsequently impaired lymphatic growth, though to a lesser degree than when all myeloid cells were removed.
- Hyaluronan is essential for promoting lymphatic cell network formation and sprouting
Hyaluronan is a key component of the extracellular matrix which has roles in regulating inflammation, including through the recruitment of immune cells (6). The authors treated macrophages with Hyaluronidase (an enzyme that breaks down hyaluronan) and found that this reduced lymphatic sprouting.
This finding is important as it suggests that the macrophages are forming direct cell-cell contacts with the endothelial cells, providing a potential mechanism of action in the developing heart lymphatics. There are a number of hyaluronan binding proteins (7) which leaves scope for future investigations into the exact mechanism at play.
Why I chose this preprint
I have a deep affection for macrophages and imaging. This work further shows just how incredible macrophages are at multitasking and is an excellent use of microscopy to reveal concepts that would be difficult to otherwise understand and observe – And of course, the images are beautiful.
Open questions
- What do the authors believe the macrophages are doing at the lymphatic branch points? Are the macrophages phagocytosing material or secreting specific cytokines or growth factors? Do the authors have further evidence that the macrophage activities dependent on cell-cell interactions as they suggest?
- If direct macrophage-endothelial cell contacts are required, how do the author propose these are mediated? Could specific genes be knocked-out to prevent this direct contact, for example E-cadherin?
References
- Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013 Apr 25;496(7446):445–55.
- A-Gonzalez N, Quintana JA, García-Silva S, Mazariegos M, Aleja AG de la, Nicolás-Ávila JA, et al. Phagocytosis imprints heterogeneity in tissue-resident macrophages. J Exp Med. 2017 Apr 20;jem.20161375.
- Ma Y, Mouton AJ, Lindsey ML. Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction. Transl Res J Lab Clin Med. 2018 Jan;191:15–28.
- Huang L-H, Lavine KJ, Randolph GJ. Cardiac Lymphatic Vessels, Transport, and Healing of the Infarcted Heart. JACC Basic Transl Sci. 2017 Aug 28;2(4):477–83.
- Liu X, Oliver G. New insights about the lymphatic vasculature in cardiovascular diseases. F1000Research [Internet]. 2019 Oct 29 [cited 2020 Aug 13];8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820817/
- Petrey AC, de la Motte CA. Hyaluronan, a Crucial Regulator of Inflammation. Front Immunol [Internet]. 2014 [cited 2020 Aug 13];5. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2014.00101/full
- Day AJ, Prestwich GD. Hyaluronan-binding Proteins: Tying Up the Giant. J Biol Chem. 2002 Feb 15;277(7):4585–8.
Posted on: 25 August 2020
doi: https://doi.org/10.1242/prelights.17797
Read preprintSign up to customise the site to your preferences and to receive alerts
Register hereAlso in the cell biology category:
BRCA1/BARD1 ubiquitinates PCNA in unperturbed conditions to promote replication fork stability and continuous DNA synthesis
Quantification of gallium cryo-FIB milling damage in biological lamella
Coordinated growth of linked epithelia is mediated by the Hippo pathway
Also in the developmental biology category:
Also in the immunology category:
Insm1 regulates the development of mTECs and immune tolerance
Intestinal lamina propria supports acquired eTreg suppressor function
An Arp2/3-cPLA2-NFκB axis acts as a Cell Shape Sensor to drive Homeostatic Migration of Dendritic Cells
preListscell biology category:
in theAlumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
List by | Nadja Hümpfer et al. |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
List by | Osvaldo Contreras |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
List by | Ana Dorrego-Rivas |
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
List by | Dey Lab, Samantha Seah |
1
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
List by | Maiko Kitaoka et al. |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.
List by | Paul Gerald L. Sanchez and Stefano Vianello |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
List by | Dey Lab |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
List by | Sandra Malmgren Hill |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
List by | Rob Hynds |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
List by | Pablo Ranea Robles |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
List by | Dey Lab |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
List by | Sandra Franco Iborra |
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
List by | Joseph Jose Thottacherry |
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
List by | Dey Lab, Amanda Haage |
Also in the developmental biology category:
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
List by | Nadja Hümpfer et al. |
2nd Conference of the Visegrád Group Society for Developmental Biology
Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)
List by | Nándor Lipták |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
List by | Osvaldo Contreras |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
List by | Alex Eve |
EMBL Conference: From functional genomics to systems biology
Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020
List by | Jesus Victorino |
Single Cell Biology 2020
A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.
List by | Alex Eve |
Society for Developmental Biology 79th Annual Meeting
Preprints at SDB 2020
List by | Irepan Salvador-Martinez, Martin Estermann |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
List by | Ana Dorrego-Rivas |
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
List by | Maiko Kitaoka et al. |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.
List by | Paul Gerald L. Sanchez and Stefano Vianello |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
List by | Madhuja Samaddar et al. |
EDBC Alicante 2019
Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.
List by | Sergio Menchero et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
List by | Dey Lab |
SDB 78th Annual Meeting 2019
A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.
List by | Alex Eve |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
List by | Rob Hynds |
Young Embryologist Network Conference 2019
Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London
List by | Alex Eve |
Pattern formation during development
The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.
List by | Alexa Sadier |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
List by | Dey Lab |
Zebrafish immunology
A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.
List by | Shikha Nayar |
Also in the immunology category:
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
List by | Osvaldo Contreras |
Single Cell Biology 2020
A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.
List by | Alex Eve |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
List by | Sandra Malmgren Hill |
Antimicrobials: Discovery, clinical use, and development of resistance
Preprints that describe the discovery of new antimicrobials and any improvements made regarding their clinical use. Includes preprints that detail the factors affecting antimicrobial selection and the development of antimicrobial resistance.
List by | Zhang-He Goh |