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Updated: May 31, 2026

Flow Cytometry Analysis of Murine Bone Marrow Hematopoietic Stem and Progenitor Cells and Stromal Niche Cells
Published on: September 28, 2022
All hematopoietic cells develop from hematopoietic stem cells through Flk2/Flt3-positive progenitor cells
Scott W Boyer1, Aaron V Schroeder, Stephanie Smith-Berdan
1Program in Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, USA.
Hematopoietic stem cells (HSCs) differentiate into all blood lineages through Flk2-expressing progenitors. HSC origin and maintenance are Flk2-independent, with lineage separation occurring after Flk2 upregulation.
Area of Science:
- Hematology
- Stem Cell Biology
- Developmental Biology
Background:
- Hematopoietic stem cells (HSCs) generate all blood cell types, but differentiation pathways beyond HSCs are debated.
- Previous studies yielded conflicting results regarding progenitor lineage potential and their contribution to multilineage differentiation.
Purpose of the Study:
- To definitively assess in vivo hematopoietic differentiation pathways.
- To clarify the role of Flk2 expression in HSC maintenance and progenitor differentiation.
Main Methods:
- Development of a novel lineage tracing mouse model for in vivo pathway assessment.
- Analysis of Flk2 expression during steady-state hematopoiesis, stress hematopoiesis, and HSC transplantation.
Main Results:
- All hematopoietic lineages, including megakaryocyte/erythroid cells, arise from Flk2-expressing, non-self-renewing progenitors.
- Hematopoietic stem cell (HSC) origin and maintenance do not involve a Flk2-expressing stage.
- Flk2 upregulation is not required for HSC specification and maintenance.
Conclusions:
- Hematopoietic lineage separation occurs downstream of Flk2 upregulation.
- HSC specification and maintenance are Flk2-independent processes.
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