Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions

Cell Stem Cell. 2015 Jul 2;17(1):35-46. doi: 10.1016/j.stem.2015.05.003. Epub 2015 Jun 18.


Despite great advances in understanding the mechanisms underlying blood production, lineage specification at the level of multipotent progenitors (MPPs) remains poorly understood. Here, we show that MPP2 and MPP3 are distinct myeloid-biased MPP subsets that work together with lymphoid-primed MPP4 cells to control blood production. We find that all MPPs are produced in parallel by hematopoietic stem cells (HSCs), but with different kinetics and at variable levels depending on hematopoietic demands. We also show that the normally rare myeloid-biased MPPs are transiently overproduced by HSCs in regenerating conditions, hence supporting myeloid amplification to rebuild the hematopoietic system. This shift is accompanied by a reduction in self-renewal activity in regenerating HSCs and reprogramming of MPP4 fate toward the myeloid lineage. Our results support a dynamic model of blood development in which HSCs convey lineage specification through independent production of distinct lineage-biased MPP subsets that, in turn, support lineage expansion and differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Cellular Reprogramming
  • Gene Expression
  • Hematopoiesis*
  • Hematopoietic Stem Cells / classification
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology
  • Lymphoid Progenitor Cells / classification
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological
  • Multipotent Stem Cells / classification*
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / physiology
  • Myeloid Progenitor Cells / classification
  • Myeloid Progenitor Cells / cytology
  • Myeloid Progenitor Cells / physiology
  • Regeneration

Associated data

  • GEO/GSE68529