Revision of the human hematopoietic tree: granulocyte subtypes derive from distinct hematopoietic lineages

Cell Rep. 2013 May 30;3(5):1539-52. doi: 10.1016/j.celrep.2013.04.025. Epub 2013 May 23.

Abstract

The classical model of hematopoiesis predicts a dichotomous lineage restriction of multipotent hematopoietic progenitors (MPPs) into common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs). However, this idea has been challenged by the identification of lymphoid progenitors retaining partial myeloid potential (e.g., LMPPs), implying that granulocytes can arise within both the classical lymphoid and the myeloid branches. Here, we resolve this issue by using cell-surface CD133 expression to discriminate functional progenitor populations. We show that eosinophilic and basophilic granulocytes as well as erythrocytes and megakaryocytes derive from a common erythro-myeloid progenitor (EMP), whereas neutrophilic granulocytes arise independently within a lympho-myeloid branch with long-term progenitor function. These findings challenge the concept of a CMP and restore dichotomy to the classical hematopoietic model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / metabolism
  • Antigens, CD34 / metabolism
  • Basophils / cytology
  • Basophils / metabolism
  • Cell Lineage
  • Cells, Cultured
  • Eosinophils / cytology
  • Eosinophils / metabolism
  • Glycoproteins / metabolism
  • Granulocytes / cytology*
  • Granulocytes / metabolism
  • Hematopoiesis
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neutrophils / cytology
  • Neutrophils / metabolism
  • Peptides / metabolism

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, CD34
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse