Saved my 1st tweet for my 1st paper and very excited to share what I’ve been working on with @ShirleyGreenba1 and @Inna_Averbukh in @MikeAngeloLab! We assembled the 1st spatio-temporal protein tissue atlas of the human maternal-fetal interface at single-cell resolution 🧵[1/9]
In pregnancy, fetal cells invade the mother’s uterus. They remodel arteries and replace part of the artery lining 🤯 This is an immunological mystery and it’s *required* for healthy pregnancy. Impaired invasion and remodeling are implicated in many pregnancy complications [2/9]
Which cells participate? How does this evolve with 1) gestational age and 2) artery remodeling? All unanswered Qs. To examine these, we used #MIBITOF to simultaneously profile 37 proteins in archival tissue from 66 patients, analyzing >500k cells and almost 600 arteries [3/9]
We find that gestational age is the main driver of immune cell composition in the 1st 20 wks of pregnancy. Earlier = more NK cells. Later = more macrophages. This correlation is so tight we were able to train a model to predict gestational age, accurate to a 19 day window! [4/9]
What about artery remodeling? Since remodeling of the arteries and gestational age are correlated, it’s challenging to distinguish features specifically unique to each 🤔🤔 However, … [5/9]
We combine manual labels with artery features extracted from the images to construct a continuous remodeling trajectory using custom machine learning techniques 🤖, allowing us to decouple immune features associated with remodeling from those associated with gestational age [6/9]
What did we learn about remodeling specifically? Remodeling is preferentially associated with the presence of invasive fetal cells in nearby tissue as well as 2 specific NK cell populations 🧐 [7/9]
We also took advantage of the spatial nature of our atlas to address a hotly debated question. What route do fetal cells take to invade arteries? 👶🏼➡️🤰🏻
Our statistical model says it’s the panel on the left 👀 [8/9]
Final message: human pregnancy is fascinating but poorly understood. We use a #singlecell approach to shed some light into unique aspects of immune changes with respect to gestational age and artery remodeling. Full paper on @biorxivpreprint! [9/9] biorxiv.org/content/10.110…
Bonus content: one advantage of MIBI is getting to stare at these beautiful images all day!
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