bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.10.16.681898

Calcium: Modulator of Post-transcriptional and post-translational process in mESCs

Sharma, S.·Palakodeti, D.·Mukherjee, T.
View original source ↗Export metadata ↓

Abstract

Calcium ion (Ca2+) is a ubiquitous intracellular and extracellular messenger that regulates several cellular activities. Previous findings have reported the presence of active Ca2+ receptors in mouse embryonic stem cells (mESCs) but the fundamental requirement of Ca2+ signalling remains unclear. We have noted the presence of high Ca2+ in undifferentiated mESCs and showed that its depletion exerts G2/M cell cycle arrest, spontaneous differentiation of mESCs towards mesoderm lineage and mitochondrial biogenesis. Further, our data demonstrates that Ca2+ regulates the homeostasis and stability of Oct4 and Nanog at the post-translational level through pCamkII dependent mechanism independent of polyubiquitin system, JAK-STAT3 pathway, transcriptional and translational control. Our data also signifies the role of Ca2+ at the post-transcriptional level in regulating p-bodies and stress granule markers (Dcp1a, XRN1, Tudor and EDC4), splicing-dependent and 3UTR-dependent NMD activity. Together, this study identifies the broad role of Ca2+ in modulating key processes in mESCs. HighlightsCa2+ is present at elevated levels in mESCs and is important for pluripotency Ca2+ depletion accelerates G2/M cell cycle arrest and mesoderm differentiation Ca2+ regulates pluripotency and p-bodies markers at the post-translational level Ca2+ regulates Oct4, Nanog, dcp1a through pCaMKII dependent mechanism

Explore related subjects

cell biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Sharma, S., Palakodeti, D., Mukherjee, T.. 2025-10-16. Calcium: Modulator of Post-transcriptional and post-translational process in mESCs. https://doi.org/10.1101/2025.10.16.681898

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Evidence of complete myofibril remodeling after severe damage in adult Drosophila.

Muscle function depends on the ability of myofibrils to withstand and repair mechanical damage, yet how adult muscles remodel damaged myofibrils remains poorly understood. Here, we establish a Drosophila model that allows the induction and longitudinal visualization of extensive myofibril damage and recovery in intact adult femur muscles. Sustained muscle depolarization caused extensive disruption of myofibrillar organization, with severe damage characterized by near-complete loss of Z-disc structures. Remarkably, myofibril architecture and muscle function were largely restored within days, revealing a substantial capacity for myofibril reconstruction in adult femur muscles. We identified two distinct states of myofibril damage, mild and severe, with mild damage appearing before severe damage during aging, suggesting a progressive process of myofibril deterioration and repair failure. We further show that filamins mechanosignaling is required for efficient myofibril remodeling. Following damage, wild-type filamin redistributes from the Z-disc and accumulates outside the myofibrils, whereas constitutively open filamin remains Z-disc-associated and constitutively closed filamin redistributes but results in increased damage and impaired recovery. These findings suggest that effective repair requires dynamic transitions between filamin conformational states and that filamin redistribution is an active component of the damage response rather than simply a consequence of muscle injury. During aging, filamin progressively redistributes from the Z-disc and muscle damage accumulates, with severe damage increasing after the appearance of mild damage. Together, our findings reveal a previously unappreciated capacity of adult muscle to reassemble damaged myofibrils and identify filamin mechanosignaling as a key component of this repair process, providing a framework for understanding how defective mechanosensing may contribute to age-related muscle decline and muscle disease.

cell biology↗
bioRxiv2026

Temporal proximity proteomics reveals ANP32A roles in replication fork progression and end joining

Acidic nuclear phosphoprotein 32 family member A (ANP32A) regulates chromatin and histone homeostasis, but its contribution to DNA replication and repair remains unclear. Time-resolved AirID proximity labeling with data-independent acquisition mass spectrometry revealed phased remodeling of the ANP32A proximal proteome during hydroxyurea-induced replication stress. Early stress enriched DNA replication and repair factors, including FEN1, XRCC5/Ku80, and XRCC6/Ku70, whereas prolonged exposure shifted the network towards checkpoint and cell-cycle regulators. Orthogonal proximity ligation assays revealed sustained ANP32A-FEN1 proximity and transiently increased ANP32A-XRCC5 proximity. ANP32A was dynamically recruited to {gamma}H2AX-marked lesions following laser microirradiation and showed increased proximity to {gamma}H2AX after hydroxyurea treatment. ANP32A loss impaired proliferation and G1/S progression and moderately reduced replication fork velocity. However, it did not promote nascent strand degradation at stalled forks or measurably alter homologous recombination reporter activity. In contrast, ANP32A loss reduced non-homologous end-joining reporter activity, consistent with its stress-induced proximity to Ku proteins. These findings identify ANP32A as a chromatin-associated factor supporting replication fork progression and end joining while dispensable for stalled-fork protection, linking ANP32A-dependent chromatin regulation to genome maintenance.

cell biology↗
bioRxiv2026

Mapping Uterine Remodeling from Pregnancy to a New Homeostatic State

Pregnancy drives uterine remodeling through rapid anatomical expansion and scar-free postpartum repair, yet how the organ reconstructs its cellular architecture after birth remains incompletely understood. Here, we present single-cell transcriptomic profiling of 698,631 cells derived from the whole mouse uterus across five distinct stages centered around parturition: Non-pregnant Control, late gestation (embryonic day 16.5), and postpartum days (PPD) 1, 7, and 30. We resolved 16 distinct cell lineages spanning epithelial, stromal, endothelial, and immune compartments. Although gross morphological involution occurs rapidly, with uterine horn length returning to baseline levels by PPD7, the underlying cellular architecture does not revert to its pre-pregnancy state. Tissue composition, transcriptional states, and intercellular signalling networks did not revert to their pre-pregnancy configurations. Instead, postpartum reconstruction proceeded through five sequential but overlapping transcriptional programs, with individual cells simultaneously extinguishing gestational programs and acquiring repair-associated states. By one month postpartum, the tissue adopts a reconfigured architecture that fails to fully reactivate the non-pregnant baseline, thus, establishing a novel homeostatic state. This work provides a foundation for delineating the specific organizational levels that fully recover following physiological injury versus those that establish new baseline set points.

cell biology↗