iiinova — where your digital self keeps evolving

James Zwierzynski @jamesbzsci.bsky.social · 08/09/2026

A wonderful past two weeks, presenting my work at the 10th Anniversary @HHMIJanelia / @embl Imaging Mouse Development Conference, submitting the DP5, and doing plenty of hiking after turning the big 3-0 and celebrating with a visit from my mom! Onto the best decade yet!

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James Zwierzynski @jamesbzsci.bsky.social · 28/08/2026

#FluorescenceFriday! Light sheet of the whole guinea pig uterus at E9.5 -epithelium (CK7, teal), smooth muscle (SMA, yellow). The middle pit is a uterine crypt where the embryo implanted and is undergoing gastrulation. These beautiful gland projections seen are key regulators of these processes too!

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James Zwierzynski @jamesbzsci.bsky.social · 28/05/2026

Looking to join a collaborative team studying coronary artery development? Love taking pretty microscope images? The Red-Horse lab(@hhmi-science.bsky.social/Stanford) is hiring for a senior scientist to research coronary & collateral artery development apply below!: tinyurl.com/5d85xjze

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

There is sparse evidence for decidual CXCR4's function, so CXCR4 activation in decidual cells surprised us. However, beautiful work out this week in Nature shows a population of CXCR4+ human decidual cells associated with blood vessels & pregnancy complications - exciting parallels to what we see!

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

We find an arterial defect emerges soon after this; we think this presents a model for understanding how early pregnancy defects manifest in late-gestation syndromes. Most importantly, we see work opening a new understanding of mouse placentation and invasion - which we can't fait to follow up on!

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

While we find many symptoms of PAS arising in these mice in late gestation, we sought to understand what the initial insult might be. Clinical hypotheses suggest defective decidualization underlies this syndrome, and we indeed find this in early gestation in our model.

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

Most surprisingly, these mice showed invasion of placental cells into the deep myometrium and myometrial arteries, a phenotype reminiscent of human placenta accreta spectrum (PAS) disorder. We validated this over-invasion using fetal cell labeling and pharmacologic approaches.

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

Interestingly, these embryos die in late gestation, but appeared grossly normal here (E12.5). 3D imaging revealed that loss of fetal Cxcl12 mispatterned the maternal-fetal interface, with arteries and trophoblasts pushed to the periphery rather than central region.

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

To test for the role of this placental Cxcl12, we deleted the fetal gene, and found hypoplastic placentas with few arteries and invasive trophoblasts. We pharmacologically validated through CXCR4 inhibition that this interaction was most essential in early pregnancy.

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

Which molecules control this growth? We found our favorite chemokine, Cxcl12, was expressed transiently in the early placenta; while its cognate maternal receptor was activated on surrounding decidual cells, and newly forming arteries.

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

As vascular biologists, we were interested in understanding where this beautiful artery growth we visualized was sourced from, and we found that they were primarily sourced from capillary progenitors undergoing an arterial fate acquisition in early pregnancy.

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

We analyzed the positions of arteries & trophoblasts, benchmarked to placental anatomical landmarks. We found that trophoblast invasion skews in random directions, not always aligned directly with artery positioning. So, individual 2D tissues sections may lie in planes which miss this nuance.

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

Why have we missed this in the mouse? A logical explanation is the optical clarity resolved by 3D imaging. However, we also found a biologically-rooted explanation – arteries persist in the mature placenta in regular patterns – but trophoblast invasion occurs with random bias.

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

Using 3D whole-organ, light sheet imaging, we find that instead trophoblast invasion is underestimated by 4-5-fold by traditional 2D analyses. Through this approach, we find a beautiful progression of arterial growth towards the placenta over gestation, accompanied by massive trophoblast invasion.

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James Zwierzynski @jamesbzsci.bsky.social · 12/04/2026

Dogma has long held that the mouse is a poor model of deep placentation that is observed in humans, due to shallow trophoblast invasion and poor arterial tropism of those trophoblasts. We wanted to test this, so I adapted an improved light-sheet imaging protocol for whole implantation sites.

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