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Updated: Aug 15, 2026
Identification and Isolation of Oligopotent and Lineage-committed Myeloid Progenitors from Mouse Bone Marrow
Published on: July 29, 2018
Heterogeneity of Flt3-expressing multipotent progenitors in mouse bone marrow
Anne Y Lai1, Simon M Lin, Motonari Kondo
1Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Abstract:
Mechanisms of lymphoid and myeloid lineage choice by hemopoietic stem cells remain unclear. In this study we show that the multipotent progenitor (MPP) population, which is immediately downstream of hemopoietic stem cells, is heterogeneous and can be subdivided in terms of VCAM-1 expression. VCAM-1(+) MPPs were fully capable of differentiating into both lymphoid and myeloid lineages. In contrast, VCAM-1(-) MPPs gave rise to lymphocytes predominately in vivo. T and B cell development from VCAM-1(-) MPPs was 1 wk faster than that from VCAM-1(+) MPPs. Furthermore, VCAM-1(+) MPPs gave rise to common myeloid progenitors and VCAM-1(-) MPPs in vivo, indicating that VCAM-1(-) MPPs are progenies of VCAM-1(+) MPPs. VCAM-1(-) MPPs, in turn, developed into lymphoid lineage-restricted common lymphoid progenitors. These results establish a hierarchy of developmental relationship between MPP subsets and lymphoid and myeloid progenitors. In addition, VCAM-1(+) MPPs may represent the branching point between the lymphoid and myeloid lineages.
Insights
Hematopoietic stem cell lineage choice is clarified by VCAM-1 expression on multipotent progenitors (MPPs). VCAM-1(-) MPPs preferentially generate lymphocytes, while VCAM-1(+) MPPs are a branching point for lymphoid and myeloid lineages.
Area of Science:
- Hematology
- Immunology
- Developmental Biology
Background:
- The mechanisms governing hematopoietic stem cell (HSC) differentiation into lymphoid and myeloid lineages are not fully understood.
- Multipotent progenitor (MPP) populations are key intermediates in HSC differentiation.
Purpose of the Study:
- To investigate the heterogeneity of the MPP population and its role in lymphoid and myeloid lineage commitment.
- To define the developmental hierarchy and lineage potential of distinct MPP subsets.
Main Methods:
- Subdivision of the MPP population based on VCAM-1 expression.
- In vivo differentiation assays to assess lineage potential.
- Analysis of progenitor development and hierarchy.
Main Results:
- The MPP population is heterogeneous, separable into VCAM-1-expressing (VCAM-1(+)) and non-expressing (VCAM-1(-)) subsets.
- VCAM-1(+) MPPs differentiate into both lymphoid and myeloid lineages.
- VCAM-1(-) MPPs predominantly generate lymphocytes in vivo, with faster T and B cell development compared to VCAM-1(+) MPPs.
- VCAM-1(+) MPPs generate common myeloid progenitors and VCAM-1(-) MPPs, establishing VCAM-1(-) MPPs as downstream progeny.
- VCAM-1(-) MPPs develop into lymphoid lineage-restricted common lymphoid progenitors.
Conclusions:
- VCAM-1 expression defines functionally distinct MPP subsets with hierarchical relationships.
- VCAM-1(+) MPPs represent a crucial branching point for lymphoid and myeloid lineage commitment.
- A developmental hierarchy exists from VCAM-1(+) MPPs to VCAM-1(-) MPPs and subsequently to lymphoid and myeloid progenitors.
