Taylor, S. V. | bioRxiv Science

bioRxiv2026

Regulation of PDGF-BB Signaling in Placental Pericytes by Soluble PDGFRβ Isoforms: Implications for Fetoplacental Vascular Development

ABSTRACT/SUMMARYVascular remodeling within the developing fetus and placenta is essential for supporting the growth and function of emerging tissues and organs. 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-EC communication is mediated in part by platelet-derived growth factor-BB (PDGF-BB) 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-placental 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-{beta} (sPDGFR{beta}) isoforms. These variants were detected at the protein and transcript levels in mouse and human placentas, as well as in a murine trophoblast-embryonic stem cell (TESC) differentiation model that recapitulates aspects of early placental vascular development. Within this model, sPDGFR{beta} 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{beta} might influence PDGF-BB signaling, we exposed TESCl-derived vascular networks to excess PDGF-BB with or without a sPDGFR{beta} mimetic. PDGF-BB alone reduced full-length PDGFR{beta} levels while increasing receptor phosphorylation, consistent with known ligand-induced regulatory mechanisms. Inclusion of the sPDGFR{beta} 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{beta} isoforms may modulate PDGF-BB 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.

developmental biology↗

bioRxiv2018

Does internal metabolic state determine human motor coordination strategy?

Motor coordination requires the orchestration of multiple degrees of freedom in order to perform actions. Humans display characteristic and predictable reaching trajectories even though multiple trajectories are possible. Computational theories of motor control can explain these reaching trajectories by assuming that subjects orchestrate their movements to minimise a cost function, such as end-point variability or movement effort. However, how internal metabolic states influence decision making and sensorimotor control is not well understood. Here we measure human behaviour during a centre out reaching task in two distinct metabolic conditions in the morning - after having had breakfast and not. We find that humans alter their patterns of motor coordination according to their internal metabolic state and that this change in behaviour results in a 20% lower task-related energy expenditure when fasted. We suggest that movements are orchestrated according to different criteria in different metabolic states so that metabolic costs are reduced in low metabolic states. We also predict that motor coordination strategies take the metabolic costs of specific muscle groups into account when planning and executing movements. Thus, metabolic state may alter the computational strategies of decision making between animal-based experiments (in typically low metabolic conditions) and human psychophysics experiments (in typically high metabolic conditions).

neuroscience↗