Spatiotemporal Proteome Remodeling Directs Human Hematopoietic Stem Cells via a Metabolic-Cytoskeletal Axis
Masoumi, Z.; Shirodkar, N.; Wheeler, L.; Guthrie, M.; Davies, D.; Hernandez, D.; Grey, W.
Show abstract
Hematopoietic stem cells (HSCs) sustain the lifelong production of all blood and immune cells and are central to transplantation and gene therapies. However, the clinical use of these approaches remains limited due to the functional attrition of HSCs during ex vivo adaptation and expansion in culture. As these transitions are executed at the protein and structural level, the primary drivers of cellular adaptation have remained elusive in transcriptional studies. Here, we overcome the technical resolution limits of rare primary cells by integrating a scalable, ultra-low input proteomics pipeline with 3D super-resolution imaging to map the proteomic and spatial organization of primary human HSCs during ex vivo expansion. Our analysis reveals a previously unrecognized, metabolic-cytoskeletal axis that coordinates organelle reorganization and structural polarity. Perturbation of this axis preserves structural polarity while uncoupling it from biomass expansion, demonstrating that growth and functional deterioration are separable processes in ex vivo HSC culture. These findings establish a framework for understanding ex vivo HSC adaptation and expansion and inform the rational development of next-generation cellular therapies.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Expression of terminal deoxynucleotidyl transferase (TdT) identifies lymphoid-primed progenitors in human bone marrow 96%
- Immunometabolic determinants of long-term response in leukemia patients receiving CD19 CAR T cell therapy 95%
- Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology 95%
Similar papers in this journal
- Automated live-cell single-molecule tracking in enteroid monolayers reveals transcription factor dynamics probing lineage-determining function 95%
- Metabolic regulation of RNA methylation by the m6A-reader IGF2BP3 95%
- A Spatiotemporal Map of Co-Receptor Signaling Networks Underlying B Cell Activation 94%
Similar papers in this journal
- Mechano-osmotic signals control chromatin state and fate transitions in pluripotent stem cells 96%
- Heat shock chaperone HSPB1 regulates cytoplasmic TDP-43 phase separation and liquid-to-gel transition 94%
- Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration 94%
Similar papers in this journal
- Alternative splicing decouples local from global PRC2 activity 95%
- Deciphering functional tumor-immune crosstalk through highly multiplexed imaging and deep visual proteomics 95%
- RAPIDASH: A tag-free enrichment of ribosome-associated proteins reveals compositional dynamics in embryonic tissues and stimulated macrophages 94%
Similar papers in this journal
- Context-Dependent Modification of PFKFB3 in Hematopoietic Stem Cells Promotes Anaerobic Glycolysis and Ensures Stress Hematopoiesis 96%
- Proteomic and functional comparison between human induced and embryonic stem cells 95%
- Joint profiling of cell morphology and gene expression during in vitro neurodevelopment 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.