New preprint🚨 We generated human brain pericytes from pluripotent stem cells. They show strong molecular & functional similarities to primary human brain pericytes Transplanted into pericyte-deficient mice, they formed hybrid human-mouse microvessels🐭 biorxiv.org/content/10.1... - ThreadSky

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rrust.bsky.social • 39 days ago

New preprint🚨 We generated human brain pericytes from pluripotent stem cells. They show strong molecular & functional similarities to primary human brain pericytes

Transplanted into pericyte-deficient mice, they formed hybrid human-mouse microvessels🐭

https://biorxiv.org/content/10.1101/2023.06.26.546577v2

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rrust.bsky.social•39 days ago

We first compared iPSC-pericytes and primary pericytes using proteomics/phosphoproteomics and found no major differences—iPSC-PC shared 96% of proteins and 98% of phosphopeptides, including key markers, adhesion proteins, and TFs.

rrust.bsky.social•39 days ago

Next we show iPSC-pericytes help with the formation of blood-brain barrier tight junction proteins in human brain endothelial cells.

rrust.bsky.social•39 days ago

Then we asked whether iPSC-pericytes can home to brain capillaries in host brains with reduced pericyte coverage. We added our cells to live brain slices of pericyte-deficient mice

rrust.bsky.social•39 days ago

To assess the specificity of homing, we downregulated PDGFRB a key pericyte surface receptor involved in cell adhesion in iPSC-pericytes (using siRNA), which resulted in reduced homing.

rrust.bsky.social•39 days ago

Next, we confirmed a functional iPSC-pericyte–vasculature association using a proximity ligation assay (PLA) targeting two known pericyte–endothelium interactions: PDGF-BB/PDGFRB and vitronectin/ITGA5

rrust.bsky.social•39 days ago

To assess if the homing effect can be also seen in vivo, we next transplanted iPSC-pericytes into the hippocampi of pericyte-deficient mice. Similar to the ex vivo results, we confirmed that iPSC-pericytes can home to brain capillaries of mice in vivo

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