Biology subjects

Baldauf, J.

Publications and source records attributed to Baldauf, J..

2 recordsLinked to original sources

bioRxiv2026

iPSC modeling of pulmonary arterial hypertension to uncover pathomechanisms and unrecognized modes of action of sotatercept

Pulmonary arterial hypertension (PAH) is a potentially fatal disease characterized by obliterative remodeling of distal pulmonary arteries, commonly associated with bone morphogenetic receptor type 2 (BMPR2) gene mutations. In patients with PAH, sotatercept, an activin signaling inhibitor, improves hemodynamics and outcomes, but clinical responses vary and sometimes occur within weeks, suggesting additional mechanisms beyond its anti-proliferative, pro-apoptotic and anti-remodeling effects. Using patient-specific induced pluripotent stem cell-derived smooth muscle cells (iSMCs) with BMPR2 extracellular- or kinase-domain mutations, we were able to reproduce Activin A-driven PAH traits, including hyperproliferation, reduced apoptosis, enhanced contraction and excessive matrix production. We identified smooth muscle cell-to-myofibroblast transition as a previously unknown contributor to pulmonary vascular remodeling and demonstrate that it is blocked by sotatercept. Beyond its established effects, sotatercept rapidly reduced contractility, collagen-integrin mechanotransduction and TGF{beta} receptor expression, disrupting a pathological positive feedback loop, reflected by lower levels of circulating TGF{beta}1 in patients on sotatercept. Taken together, our patient-derived iSMC platform links mutation-dependent mechanisms of pulmonary vascular remodeling to variable drug responsiveness and reveals previously unrecognized, potentially rapid-acting modes of sotatercept in PAH. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/711267v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@18d5e53org.highwire.dtl.DTLVardef@2bc80dorg.highwire.dtl.DTLVardef@5ace98org.highwire.dtl.DTLVardef@1b16171_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2017

Root type and soil phosphate determine the taxonomic landscape of colonizing fungi and the transcriptome of field-grown maize roots

Key findingOur data illustrates for the first time that root type identity and phosphate availability determine the community composition of colonizing fungi and shape the transcriptomic response of the maize root system.\n\nSummaryO_LIPlant root systems consist of different root types colonized by a myriad of soil microorganisms including fungi, which influence plant health and performance. The distinct functional and metabolic characteristics of these root types may influence root type inhabiting fungal communities.\nC_LIO_LIWe performed internal transcribed spacer (ITS) DNA profiling to determine the composition of fungal communities in field-grown axial and lateral roots of maize (Zea mays L.) and in response to two different soil phosphate (P) regimes. In parallel, these root types were subjected to transcriptome profiling by RNA-Seq.\nC_LIO_LIWe demonstrated that fungal communities were influenced by soil P levels in a root type-specific manner. Moreover, maize transcriptome sequencing revealed root type-specific shifts in cell wall metabolism and defense gene expression in response to high phosphate. Furthermore, lateral roots specifically accumulated defense related transcripts at high P levels. This observation was correlated with a shift in fungal community composition including a reduction of colonization by arbuscular mycorrhiza fungi as observed in ITS sequence data and microscopic evaluation of root colonization.\nC_LIO_LIOur findings point towards a diversity of functional niches within root systems, which dynamically change in response to soil nutrients. Our study provides new insights for understanding root-microbiota interactions of individual root types to environmental stimuli aiming to improve plant growth and fitness.\nC_LI

microbiology↗