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Heterogeneity and hierarchy of hematopoietic stem cells

Authors
  • Ema, Hideo
  • Morita, Yohei
  • Suda, Toshio1, 2, 3, 4, 5
  • 1 Department of Cell Differentiation
  • 2 Sakaguchi Laboratories of Developmental Biology
  • 3 Keio University School of Medicine
  • 4 Leibniz Institute for Age Research
  • 5 Fritz Lipmann Institute
Type
Published Article
Journal
Experimental Hematology
Publisher
Elsevier
Publication Date
Jan 01, 2014
Accepted Date
Nov 04, 2013
Volume
42
Issue
2
Pages
74–82
Identifiers
DOI: 10.1016/j.exphem.2013.11.004
Source
Elsevier
License
Unknown

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.

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