Several reports have tried to discriminate ST-HSCs and MPPs by using low or negative expression of CD4, CD11b, and/or Thy1.1, and showed some difference in duration and magnitude of reconstitution ( Morrison and Weissman, 1994 Morrison et al., 1997).
On the other hand, the Thy1.1 −, CD34 + or Flt3 +LSK fraction is capable of only transient reconstitution, thereby contains short-term (ST) HSCs or multipotent progenitors (MPPs) ( Morrison and Weissman, 1994 Osawa et al., 1996 Adolfsson et al., 2001 Christensen and Weissman, 2001). At the single cell level, ∼20% of Thy1.1 lo or ∼35% of CD34 − LSK cells display multilineage long-term reconstitution in competitive reconstitution assays ( Osawa et al., 1996 Wagers et al., 2002). The Thy1.1 lo or the CD34 − LSK fraction constitutes only ∼0.01% of total bone marrow cells. Within the LSK population, the most primitive self-renewing HSCs with long-term reconstituting activity (LT-HSCs) reside in the Thy1.1 lo, CD34 −, fms-like tyrosine kinase-3 (Flt3) − or Hoechst low (side population SP) fraction ( Morrison and Weissman, 1994 Osawa et al., 1996 Goodell et al., 1997 Adolfsson et al., 2001). In murine hematopoiesis, cells with multipotent activity reside in a small fraction of bone marrow, which lacks the expression of lineage-affiliated surface markers (Lin) but expresses high levels of Sca-1 and c-Kit ( Spangrude et al., 1988 Ikuta and Weissman, 1992). In this review, we summarize what we have learned from recent studies concerning the developmental sequences in murine and human hematopoiesis. Furthermore, it is now clear that there are considerable differences in distribution of surface markers between human and mouse hematopoiesis, which makes identification of human counterparts of mouse progenitors difficult. Importantly, prior to proceed into the classical myeloid vs lymphoid pathways, HSCs appear to form myelo-erythroid vs myelo-lymphoid progenitors ( Arinobu et al., 2007). Recent progresses in the fluorescence-activated cell sorting analysis using additional surface markers for early hematopoiesis, however, have provided more detailed developmental map downstream of HSCs.
The successful isolation of the common lymphoid progenitor (CLP) that can generate all lymphoid types but not any myeloid cells, and its counterpart, the common myeloid progenitor (CMP) that can be a source of all myeloid cell types, supports the concept that lymphoid and myeloid lineages develop independently downstream of HSCs ( Kondo et al., 1997 Akashi et al., 2000). HSCs were identified within the ‘LSK’ (Lin −Sca-1 +c-Kit +) population of the mouse bone marrow ( Spangrude et al., 1988 Morrison and Weissman, 1994 Osawa et al., 1996), and subsequently lineage-restricted progenitors at various developmental stages have been isolated downstream of HSCs by using the multicolor fluorescence-activated cell sorting system. These two lineages have been thought to use separate differentiation pathways. The lymphoid lineage consists of T, B and natural killer (NK) cells, while the myeloid lineage includes a number of morphologically, phenotypically and functionally distinct cell types such as different subclasses of granulocytes (neutrophils, eosinophils and basophils), monocytes–macrophages, erythrocytes, megakaryocytes and mast cells. Mature hematopoietic cells are traditionally categorized into two distinct lineages: the lymphoid and the myeloid. Hematopoietic stem cells (HSCs) can self-renew, and differentiate into all types of blood cells throughout life.