Multi-omics analyses reveal environmentally adaptive cell-state remodeling during human iPSC biomanufacturing

Abstract

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.

Integrated physiological and transcriptomic analyses reveal cell wall remodeling underlying firmness retention in a firm-fruited blueberry genotype
Bowei Wang, Chenxin Yu, Yibo Ma +3
Frontiers in Plant Science8 Oct 2026Peer-reviewedCC BY 4.0Full textPlant biologyCrossrefEurope PMC
Physiological and Proteomic Analyses Reveal the Adaptive Mechanisms of Maize Genotypes Under Potassium Deficiency
Xudong Yang, Haoran Qin, Fei Zou +4
International Journal of Molecular Sciences17 Sep 2026Peer-reviewedCC BY 4.0Plant biologyCrossref
Pangenome and transcriptome analyses reveal extensive diversity and breeding signatures in the oat GDSL-esterase/lipase gene family
T. Hämälä, S. Viitala
bioRxiv28 Sep 2026PreprintAll rights reservedFull textGenetics & genomicsbioRxiv
Integrative Phytochemical, Morphological and Molecular Analyses Reveal Intraspecific Diversification in Wild Iranian Populations of Heracleum persicum Desf. ex Fischer
Sima Sadat Rafiei, Kazem Mahdigholi, Mohsen Falahati-Anbaran
Plants (Basel, Switzerland)1 Oct 2026Peer-reviewedCC BYFull textPlant biologyEurope PMC
Integrated Physiological, Transcriptomic, and Proteomic Analyses Reveal Alkali Stress Response and Tolerance Mechanisms of Rhododendron obtusum ‘Fenzhuanglou’ Seedlings
Riwen Fei, Xiao Yang, Xinyue Liu +4
Plants (Basel, Switzerland)1 Oct 2026Peer-reviewedCC BYFull textPlant biologyEurope PMC

Cite

BibTeX RIS

BibTeX

@misc{colter2026multiomics,
  title = {{Multi-omics analyses reveal environmentally adaptive cell-state remodeling during human iPSC biomanufacturing}},
  author = {J. Colter and T. Dang and E. Gysel and D. Young and A. Dufour and I. Lewis and K. Murari and M. S. Kallos},
  howpublished = {bioRxiv},
  year = {2026},
  month = may,
  doi = {10.64898/2026.05.26.727850},
  url = {https://www.biorxiv.org/content/10.64898/2026.05.26.727850v3},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Multi-omics analyses reveal environmentally adaptive cell-state remodeling during human iPSC biomanufacturing
AU  - J. Colter
AU  - T. Dang
AU  - E. Gysel
AU  - D. Young
AU  - A. Dufour
AU  - I. Lewis
AU  - K. Murari
AU  - M. S. Kallos
PY  - 2026
DA  - 2026/05/26
PB  - bioRxiv
DO  - 10.64898/2026.05.26.727850
UR  - https://www.biorxiv.org/content/10.64898/2026.05.26.727850v3
AB  - 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.
ER  -

Abstract

Related

Cite