A blood capillary plexus-derived population of progenitor cells contributes to genesis of the dermal lymphatic vasculature during embryonic development

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dc.contributor.authorPichol-Thievend, C.
dc.contributor.authorBetterman, K.L.
dc.contributor.authorLiu, X.
dc.contributor.authorMa, W.
dc.contributor.authorSkoczylas, R.
dc.contributor.authorLesieur, E.
dc.contributor.authorBos, F.L.
dc.contributor.authorSchulte, D.
dc.contributor.authorSchulte-Merker, S.
dc.contributor.authorHogan, B.M.
dc.contributor.authorOliver, G.
dc.contributor.authorHarvey, N.L.
dc.contributor.authorFrancois, M.
dc.date.issued2018
dc.description.abstractDespite the essential role of the lymphatic vasculature in tissue homeostasis and disease, knowledge of the organ-specific origins of lymphatic endothelial progenitor cells remains limited. The assumption that most murine embryonic lymphatic endothelial cells (LECs) are venous derived has recently been challenged. Here, we show that the embryonic dermal blood capillary plexus constitutes an additional, local source of LECs that contributes to the formation of the dermal lymphatic vascular network. We describe a novel mechanism whereby rare PROX1-positive endothelial cells exit the capillary plexus in a Ccbe1-dependent manner to establish discrete LEC clusters. As development proceeds, these clusters expand and further contribute to the growing lymphatic system. Lineage tracing and analyses of Gata2-deficient mice confirmed that these clusters are endothelial in origin. Furthermore, ectopic expression of Vegfc in the vasculature increased the number of PROX1-positive progenitors within the capillary bed. Our work reveals a novel source of lymphatic endothelial progenitors employed during construction of the dermal lymphatic vasculature and demonstrates that the blood vasculature is likely to remain an ongoing source of LECs during organogenesis, raising the question of whether a similar mechanism operates during pathological lymphangiogenesis.
dc.description.statementofresponsibilityCathy Pichol-Thievend, Kelly L. Betterman, Xiaolei Liu, Wanshu Ma, Renae Skoczylas, Emmanuelle Lesieur, Frank L. Bos, Dorte Schulte, Stefan Schulte-Merker, Benjamin M. Hogan, Guillermo Oliver, Natasha L. Harvey, and Mathias Francois
dc.identifier.citationDevelopment, 2018; 145(10):dev160184-1-dev160184-14
dc.identifier.doi10.1242/dev.160184
dc.identifier.issn0950-1991
dc.identifier.issn1477-9129
dc.identifier.orcidHarvey, N.L. [0000-0001-9839-8966]
dc.identifier.urihttp://hdl.handle.net/2440/113297
dc.language.isoen
dc.publisherThe Company of Biologists
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1107643
dc.relation.granthttp://purl.org/au-research/grants/arc/DP150103110
dc.relation.grantR01-HL073402
dc.relation.granthttp://purl.org/au-research/grants/arc/FT130101254
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1111169
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1083811
dc.rights© 2018. Published by The Company of Biologists Ltd
dc.source.urihttps://doi.org/10.1242/dev.160184
dc.subjectLymphatic endothelial cells; skin; lymphangiogenesis; PROX1; lineage tracing; progenitor cell; mouse genetics
dc.titleA blood capillary plexus-derived population of progenitor cells contributes to genesis of the dermal lymphatic vasculature during embryonic development
dc.typeJournal article
pubs.publication-statusPublished

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