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Pericytes (PCs) play a central role in stabilizing and maturing microvascular networks by extending along endothelial cells (ECs) and reinforcing vessel integrity. In the placenta, as in other organs, PC\u2013EC communication is mediated in part by platelet-derived growth factor-BB (PDGF\u2011BB) signaling, which governs PC differentiation, proliferation, migration, and survival, ultimately enabling their recruitment and retention along capillaries. In this study, we identified progressive PC investment along feto\u2011placental capillaries in both murine and human tissues across gestation, supported by morphological and molecular evidence. Placental PCs displayed phenotypic heterogeneity comparable to that observed in the brain and heart, suggesting conserved diversity across organ systems. In addition to characterizing PC dynamics, we examined the expression of recently identified soluble PDGF Receptor-\u03b2 (sPDGFR\u03b2) isoforms. These variants were detected at the protein and transcript levels in mouse and human placentas, as well as in a murine trophoblast\u2011embryonic stem cell (TESC) differentiation model that recapitulates aspects of early placental vascular development. Within this model, sPDGFR\u03b2 expression was independent of ADAM10 activity and exogenous growth factors during early vessel formation but was markedly upregulated during hypoxia. To assess how elevated sPDGFR\u03b2 might influence PDGF\u2011BB signaling, we exposed TESC\u2011derived vascular networks to excess PDGF\u2011BB with or without a sPDGFR\u03b2 mimetic. PDGF\u2011BB alone reduced full\u2011length PDGFR\u03b2 levels while increasing receptor phosphorylation, consistent with known ligand\u2011induced regulatory mechanisms. Inclusion of the sPDGFR\u03b2 mimetic shifted these responses toward baseline, suggesting a potential modulatory or feedback role for soluble receptor variants. Together, these findings demonstrate that PCs are progressively recruited to placental capillaries and exhibit diverse phenotypes during development, and that soluble PDGFR\u03b2 isoforms may modulate PDGF\u2011BB signaling in a manner sensitive to oxygen tension. Understanding these mechanisms provides insight into the regulation of placental vascular maturation and may inform strategies to improve human health by targeting disorders rooted in impaired placental development.<\/jats:p>","DOI":"10.1007\/s10456-026-10091-3","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:37:02Z","timestamp":1788453422000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of PDGF-BB signaling in placental pericytes by soluble PDGFR\u03b2 isoforms: implications for fetoplacental vascular development"],"prefix":"10.1007","volume":"29","author":[{"given":"Audra R.","family":"Barnes-Lanier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C.","family":"Duggan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reese A.","family":"Dunkenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe V.","family":"Lessard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Cosma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chase R.","family":"Steele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah V.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan A.","family":"Darden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan D.","family":"Whitham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison R.","family":"Durica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Chappell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"10091_CR1","doi-asserted-by":"publisher","unstructured":"Woods L, Perez-Garcia V, Hemberger M (2018) Regulation of Placental Development and Its Impact on Fetal Growth\u2014New Insights From Mouse Models. 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