Functionally distinct subsets of lineage-biased multipotent progenitors control blood production in normal and regenerative conditions

By E. Pietras, Damien Reynaud, Yoon-A Kang, Daniel E. Carlin, F. Calero-Nieto, A. Leavitt, Joshua M. Stuart, Berthold Göttgens, E. Passegué. Cell Stem Cell, 2015

637 citations recorded by the source corpus.

SUMMARY 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 towards 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.

Subfields: Cell Biology, Hematology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f78dd74cba33d8654e3068a994c37d3bb85f3a6a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

In Hematology

E. Laurenti

In Molecular Biology

Citations in the corpus

Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity (2018, background): “In contrast, we found no significant difference in the lymphoidbiased MPP4 (Flt3CD48CD150 LSK) subset (Pietras et al., 2015) (Figures 1D and 1E).”
A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation. (2016, methodology): “Each cell was also stained with 3 additional antibodies against CD150,CD48, andEPCR to retrospectively assign cells to other commonly used sorting schemes for populations such as E-SLAM(3) or MPP subpopulations.(27,29) Single cells were processed for RNA-Seq as described(21) with 156 HSCs, 701 HSPCs”
The lung is a site of platelet biogenesis and a reservoir for hematopoietic progenitors (2017, neutral): “3k) 23 .”
Lineage tracing on transcriptional landscapes links state to fate during differentiation (2018, background): “In hematopoiesis, clonal tracing studies have shown evidence of functional lineage priming of multipotent progenitor cells (MPPs) 32 .”