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Reposted by Emma Haberman

Dave Grainger @degrainger.bsky.social · 18/05/2025

Great weekend celebrating @emmarose64.bsky.social's graduation with friends and family. Very proud! 😊

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Dave Grainger @degrainger.bsky.social · 13/01/2025

A huge thank you to all my co-authors, particularly Irina Lupu, Nils Kirschnick, @oliverastone.bsky.social and Friedemann Kiefer I am grateful to have been part of a project that opens so many exciting questions for the field For more details, please read our paper: doi.org/10.1038/s441...

doi.org

Direct specification of lymphatic endothelium from mesenchymal progenitors - Nature Cardiovascular Research

Lupu, Grainger, Kirschnick et al. show that, contrary to prevailing belief, the initial specification of mammalian lymphatic endothelial cells primarily occurs from previously unidentified mesenchymal...

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Dave Grainger @degrainger.bsky.social · 13/01/2025

Finally, our proposed model showing LEC differentiation through in situ specification from ETV2+PROX1+ paraxial mesoderm-derived lymphangioblasts

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Dave Grainger @degrainger.bsky.social · 13/01/2025

HCR (@hcrimaging.bsky.social) stainings suggest VEGFC/VEGFR3 signaling acts upstream of PROX1 In the absence of VEGFC/VEGFR3 signaling, specification of LECs from PXM stalls at the angioblast stage with Vegfc-/- embryos having more Etv2+Prox1- cells in the HDM.

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Dave Grainger @degrainger.bsky.social · 13/01/2025

If migrating venous ECs are the major source of LECs, a substantial increase in EC numbers would be required to maintain venous integrity. Analysis of cell cycle phase suggests angioblast-derived LECs and not venous ECs, are proliferative enough to support the rapid expansion of LECs.

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Dave Grainger @degrainger.bsky.social · 13/01/2025

Conditional lineage tracing analyses using an inducible Pax3-CreERT2 line further highlighted the transient nature of this progenitor source, and demonstrated that lymphangioblasts give rise to LECs in various tissues.

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Dave Grainger @degrainger.bsky.social · 13/01/2025

To better characterise lymphangioblast specification from PXM we performed snMultiome (RNA & ATAC) on Pax3-lineage progenitors and ECs at E9.5. SCENIC+ analysis showed GRNs formed by known (ETV2/SOX18) and novel (EBF1/2) regulators of EC/LEC specification & differentiation in lymphangioblasts

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Dave Grainger @degrainger.bsky.social · 13/01/2025

IF and HCR (@hcrimaging.bsky.social) staining of wholemount and vibratome sectioned E9.5 embryos identified lymphangioblasts as residing immediately dorsal to the cardinal vein in the Lbx1+ hypaxial dermomyotome in a pattern reminiscent of LECs migrating from the cardinal vein

Left side shows confocal images of immunostained transverse vibratome sections from E9.5 mouse embryos. In green, endothelial cells of the cardinal vein (CV) and dorsal aorta (DA) are labelled with EMCN. Pax3-Cre lineage labelled lymphangioblasts are stained for ETV2 and PROX1 dorsal to the CV. On the right, an RNA-FISH stained embryo is shown in wholemount. Endothelial cells, stained in green with Pecam1 are throughout the embryo, Lbx1+ hypaxial dermomyotome is shown in the ventral aspect of somites. A boxed region of ~4th somite is enhanced to the right showing Etv2+ lymphangioblasts within the hypaxial dermomyotome.

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Dave Grainger @degrainger.bsky.social · 13/01/2025

Surprisingly, we identified a population of cells that express both the angioblast marker Etv2 and the master regulator of LEC fate, Prox1. We have termed these cells lymphangioblasts.

Scientific figure showing force atlas embedding of scRNA-seq data with cells coloured by celltype (e.g. LEC, angioblast, arterial EC) at the top and coloured by Etv2, Pecam1 or Prox1 expression on the bottom

Scatter plot showing the expression levels of Etv2 and Prox1 from scRNA-seq data with a small population of double poitive cells highlighted in blue

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Dave Grainger @degrainger.bsky.social · 13/01/2025

The prevailing model was that PXM-derived cells contribute to venous endothelium and then transdifferentiate to LECs Irina Lupu's postdoc in Ollie's newly established lab aimed to define molecular features that may drive PXM's LEC competence using scRNA-seq on sorted EC and progenitor populations

Timeline of mouse embryonic development between embryonic day 9.5 and 11.5. Each timepoint has a schematic of a mouse embryo with paraxial mesoderm derived (Pax3-Cre;Rosa26-tdTomato) tissues (e.g. somites) in magenta and non-PXM derived ECs in green. Below the timeline arrows show that endothelial cells are FACS sorted for scRNA-seq.

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Dave Grainger @degrainger.bsky.social · 13/01/2025

✨Excited to share our work revisiting the developmental origins of mammalian lymphatic endothelial cells.✨ A summary of our key findings using scRNA-seq, snMultiome-seq and imaging to show the direct specification of mesenchymal progenitors to LECs🧵 #blutorial #blabstract tinyurl.com/LECspec

tinyurl.com

Direct specification of lymphatic endothelium from mesenchymal progenitors - Nature Cardiovascular Research

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Dave Grainger @degrainger.bsky.social · 03/12/2024

I'm not saying I spend too much time on the microscope but I can't help seeing blood vessels in christmas lights

A large tree at night covered in white Christmas lights

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