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Updated: May 5, 2026
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Flow Cytometry Analysis of Murine Bone Marrow Hematopoietic Stem and Progenitor Cells and Stromal Niche Cells
Published on: September 28, 2022
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Single-cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions
Laila Karra1, Anna-Marie Finger1, Lauren A Shechtman1
1Department of Anatomy, University of California, San Francisco, San Francisco, CA.
Blood Advances
|July 30, 2025
Summary
Aberrant Ras signals in myeloid leukemia impact hematopoietic stem cells (HSCs). Different Ras mutations uniquely affect HSC frequency, metabolism, and lineage potential, revealing distinct disease mechanisms.
Area of Science:
- Hematology
- Molecular Biology
- Cancer Biology
Background:
- Aberrant Ras signaling is common in myeloid leukemias, impacting normal hematopoiesis.
- Hematopoietic stem cells (HSCs) require balanced metabolism and protein translation for regulated blood cell production.
- The specific effects of Ras pathway mutations on rare HSCs remain largely uncharacterized.
Purpose of the Study:
- To investigate how oncogenic KRasG12D and RasGRP1 overexpression affect HSC frequency, lineage potential, and metabolism.
- To compare the impact of distinct Ras pathway lesions on normal hematopoiesis at single-cell resolution.
Main Methods:
- Single-cell proteomics and computational analyses were employed.
- Mass cytometry (CyTOF) and SCENITH (protein translation quantification) were utilized.
- Temporal proteomics and metabolomics datasets were generated.
Main Results:
- Both KRasG12D and RasGRP1 induced myeloid cell expansion but had opposing effects on HSC and progenitor populations (expansion vs. depletion).
- Both lesions elevated metabolic signals (SCENITH) in immature hematopoietic cells.
- RasGRP1 overexpression allowed for a quiescent HSC fraction, while KRASG12D did not.
Conclusions:
- The specific Ras lesion identity and duration profoundly influence HSC maintenance and lineage potential.
- Distinct Ras pathway alterations lead to unique alterations in hematopoietic stem cell function and metabolism.
- Mechanistic insights into altered hematopoiesis were gained at single-cell resolution.
