Biology subjects

Colter, J.

Publications and source records attributed to Colter, J..

2 recordsLinked to original sources

bioRxiv2026

Multi omics reveals mesodermal fate bias and enables predictive cell state control in human pluripotent stem cell biomanufacturing

Human induced pluripotent stem cells can retain conventional markers of pluripotency while acquiring environmentally dependent molecular states that may influence their developmental competence. Yet, how biomanufacturing conditions reorganize the interconnected networks governing cell state remains poorly characterized. Here, we first examined compensation of hiPSCs to static aggregation and dynamic agitation by proteomics. We then examined hiPSCs during single-passage culture in stirred-suspension bioprocesses under varying oxygen and agitation conditions. Intracellular metabolomic and transcriptomic profiling revealed distinct responses across culture configuration, hydrodynamic exposure, and oxygenation. Transition into dynamic culture broadly remodeled mitochondrial organization, carbon allocation, mechanotransduction, proteostasis, and developmental regulation. Increasing agitation produced a persistent response involving cellular architecture, growth-factor signaling, genome maintenance, and Epiblast- and lineage-aligned programs, whereas oxygenation elicited a smaller and more transient metabolic and transcriptional response. Through comparison with a human gastrulation reference, we show that these adaptations intersect with natural developmental programs without reproducing coherent epiblast state or lineage commitment. These findings demonstrate that bioprocess conditions can preserve core pluripotent identity while remodeling broader molecular states associated with developmental responsiveness, providing perspective on evaluating and optimizing hiPSC quality in biomanufacturing beyond restricted marker panels.

bioengineering↗

bioRxiv2026

Online characterization of surrogate metrics for metabolic phenotype in human induced pluripotent stem cell bioprocessing

Human induced pluripotent stem cells (hiPSCs) are the most accessible source material for derivation of stem-cell-based therapies at scale. However, a disconnect exists between quality characteristics of phenotype in the pluripotent state, and downstream metrics for efficacy and safety. Bridging this gap is a major challenge. Given hiPSC plasticity, environmental conditioning plays a crucial role in guiding phenotype. This work presents a parallelizable scale-down approach, acquiring real-time data to inform hiPSC phenotype throughout biomanufacturing. We developed an optoelectronic instrumentation suite capable of measuring pH, dissolved oxygen, and cell density as important surrogates for phenotype in a scale-down expansion bioprocess. We were successful in obtaining continuous, integrated parametric data throughout cultivation and estimating metabolic characteristics of hiPSC phenotype. This system functions as a proof-of-concept tool for development of predictive models and monitoring strategies around the elucidation of phenotypic dynamics within hiPSC biomanufacturing. We have demonstrated a feasible open-source multivariate continuous monitoring approach at research scale that combines common process parameters with a scattering measurement against aggregate density. The combination of these parameters enables surrogate measurement of a metric for metabolic phenotype. This contribution emphasizes monitoring how the bioprocess influences variables important in the context of cell state, in broader pursuit of better understanding the link to downstream functionality and global optima in hiPSC biomanufacturing for regenerative medicine.

bioengineering↗