title: Heterogeneity and hierarchy of hematopoietic stem cells.
abstract: Hematopoietic stem cells (HSCs) are a more heterogeneous population than previously thought. Extensive analysis of reconstitution kinetics after transplantation allows a new classifications of HSCs based on lineage balance. Previously unrecognized classes of HSCs, such as myeloid- and lymphoid-biased HSCs, have emerged. However, varying nomenclature has been used to describe these cells, promoting confusion in the field. To establish a common nomenclature, we propose a reclassification of short-, intermediate-, and long-term (ST, IT, and LT) HSCs defined as: ST < 6 months, IT > 6 months, and LT > 12. We observe that myeloid-biased HSCs or α cells overlap with LT-HSCs, whereas lymphoid-biased HSCs or γ/δ cells overlap with ST-HSCs, suggesting that HSC lifespan is linked to cell differentiation. We also suggest that HSC heterogeneity prompts reconsideration of long-term (>4 months) multilineage reconstitution as the gold standard for HSC detection. In this review, we discuss relationships among ST-, IT-, and LT-HSCs relevant to stem cell heterogeneity, hierarchical organization, and differentiation pathways.
authors.affiliation: Department of Cell Differentiation, Sakaguchi Laboratories of Developmental Biology, Keio University School of Medicine, Tokyo, Japan. Electronic address: hema@a7.keio.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Ema
authors.affiliation: Leibniz Institute for Age Research, Fritz Lipmann Institute, Jenna, Germany.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Morita
authors.affiliation: Department of Cell Differentiation, Sakaguchi Laboratories of Developmental Biology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
mesh_terms: D002454:Cell Differentiation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008954:Models, Biological