Distinct Hematopoietic Stem Cell Subtypes Are Differentially Regulated by TGFβ1

By Grant A. Challen, Nathan C. Boles, S. M. Chambers, Margaret A. Goodell. Cell Stem Cell, 2010

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Summary The traditional view of hematopoiesis has been that all the cells of the peripheral blood are the progeny of a unitary homogeneous pool of hematopoietic stem cells (HSCs). Recent evidence suggests that the hematopoietic system is actually maintained by a consortium of HSC subtypes with distinct functional characteristics. We show here that myeloid-biased HSCs (My-HSCs) and lymphoid-biased (Ly-HSCs) can be purified according to their capacity for Hoechst dye efflux in combination with canonical HSC markers. These phenotypes are stable under natural (aging) or artificial (serial transplantation) stress and are exacerbated in the presence of competing HSCs. My- and Ly-HSCs respond differently to TGFβ1, presenting a possible mechanism for differential regulation of HSC subtype activation. This study demonstrates definitive isolation of lineage-biased HSC subtypes and contributes to the fundamental change in view that the hematopoietic system is maintained by a continuum of HSC subtypes, rather than a functionally uniform pool.

Subfields: Hematology, Immunology

View Paper: https://www.semanticscholar.org/paper/66be2194213a6b751a3835dc33a897e338c2b4f9

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Citations in the corpus

Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal (2014, methodology): “HSCs throughout this study were purified as side population (SP)-KLS (c-kit, lineage, and Sca1)-CD150 (see the Experimental Procedures) because these are found in both young and aged mice and have high phenotypic homogeneity and functional activity (Challen et al., 2010; Mayle et al., 2013).”
Functionally distinct subsets of lineage-biased multipotent progenitors control blood production in normal and regenerative conditions (2015, positive): “Consistent with this idea, myeloid-biased HSCs have been prospectively identified based on Hoechst dye exclusion (Challen et al., 2010) or high CD150 expression (Morita et al.”
SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors (2013, background): “HSCs are also heterogeneous with respect to the ratio of myeloid to lymphoid cells that they generate upon transplantation into irradiated mice (Müller-Sieburg et al., 2002; Dykstra et al., 2007; Kent et al., 2009; Beerman et al., 2010; Challen et al., 2010; Morita et al., 2010) and with respect to ”
Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells (2015, background): “Given that HSCs are functionally heterogeneous as revealed through transplantation studies (Dykstra et al. 2007; Challen et al. 2010; Muller-Sieburg et al. 2012), wehypothesized that this retrospective variability (assessed through the outcome of a transplant) would be prospectively reflected in…”
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age (2011, background): “In mice, small numbers of myeloid-biased HSC can be found among balanced-potential HSC in young 2-mo-old mice (8, 11, 12), suggesting that the young mouse HSC pool may contain lineagebiased clones that compete for niches and expansion signals.”
Dnmt3a is essential for hematopoietic stem cell differentiation (2011, methodology): “Final gene lists were further filtered to remove sex chromosome genes, as the genders of donor HSCs were not matched, and genes significantly different between control HSCs and non-transplanted, wild-type HSC”