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Typus
Verschleierung
Bearbeiter
Hindemith
Gesichtet
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Untersuchte Arbeit:
Seite: 14, Zeilen: 1-30
Quelle: Iwasaki and Akashi 2007
Seite(n): 6692, 6693, Zeilen: 6692: l.col: 42-46, 52-59 - r.col: 1-31; 6693: l.col: 1-4
1.2.2. The subsets of human lymphoid and myeloid progenitor.

The existence of lymphoid-committed progenitors in the human bone marrow with the hCD34+CD38+CD45RA+CD10+ phenotype has been reported.42 In human cord blood, common lymphoid progenitors (CLP) activity is found in the CD7+ fraction of CD34+CD38-CD45RA+ population. The hCD34+CD38- CD45RA+CD7+ population do not exist in the adult bone marrow.43 IL-7Rα, a critical marker for the murine CLP, is expressed in human hCD10+ CLPs in the bone marrow, but not in hCD7+ CLPs in the cord blood. These data suggest that the CLP phenotype and the requirement of IL-7 signaling might have changed during the human ontogeny. In the myelo-erythroid pathway, CMP, GMP and MEP subsets can be isolated from the hCD34+CD38+ fraction in both the bone marrow and cord blood (Manz et al., 2002). All these fractions of cells are negative for the early lymphoid markers hCD10, hCD7 or hIL-7Rα. These myelo-erythroid progenitors can be prospectively isolated according to the expression of hCD45RA and hIL-3Rα. CD45RA-hIL-3Rαlo (CMPs), hCD45RA+hIL-3Rαlo (GMPs) and hCD45RA-hIL-3Rα(MEPs) efficiently form distinct myelo-erythroid colony types according to their definitions (Fig.1.1.2). CMPs give rise to MEPs and GMPs in vitro, and a significant proportion of CMPs possess clonal GM and MegE potentials.44 Thus, the hierarchical myeloid progenitor relationships demonstrated in mice is well preserved in human haematopoiesis.

Phenotypic comparisons between mouse and human subsets show that CD34, a marker positive only for murine CMPs and GMPs, is uniformly expressed on all three human subsets, and that the FcγRII/III (CD16/CD32), marking murine CMPs and GMPs, was not detectable in any of the human myeloid progenitors44 All haemato/lymphoid progenitors develop from CD34+CD38- HSC population 41but themselves have no self-renewal activity in xenogenic transplantation models 45, indicating that they are downstream of human LTHSCs in both the bone marrow and the cord blood.

Flt3 shows a significant difference in its distribution in human and mouse hematopoiesis. This suggests a critical role of Flt3 signaling in hematopoietic [development in humans.]


41. Ishikawa F, Yasukawa M, Lyons B, et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood. 2005;106:1565-1573.

42. Galy AH, Cen D, Travis M, Chen S, Chen BP. Delineation of T-progenitor cell activity within the CD34+ compartment of adult bone marrow. Blood. 1995;85:2770-2778.

43. Hao Z, Rajewsky K. Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow. J Exp Med. 2001;194:1151-1164.

44. Manz MG, Miyamoto T, Akashi K, Weissman IL. Prospective isolation of human clonogenic common myeloid progenitors. Proc Natl Acad Sci U S A. 2002;99:11872-11877.

45. Ishikawa F, Niiro H, Iino T, et al. The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways. Blood. 2007;110:3591-3660.

Human lymphoid and myeloid progenitor subsets within the hCD34+hCD38+ MPP fraction

Galy et al. (1995) first reported the existence of lymphoid-committed progenitors in the human bone marrow with the hCD34+hCD38+hCD45RA+hCD10+ phenotype. [...] In human cord blood, CLP activity is found in the hCD7+ fraction of hCD34+hCD38-hCD45RA+ population (Hao et al., 2001). Interestingly, the hCD7+ hCD34+hCD38-hCD45RA+ population does not exist in the adult bone marrow (Hao et al., 2001). IL-7Rα, a critical marker for the murine CLP, is expressed in human hCD10+ CLPs in the bone marrow, but not in hCD7+ CLPs in the cord blood. These data suggest that the CLP phenotype and the requirement of IL-7 signaling may change during human ontogeny.

In the myelo-erythroid pathway, CMP, GMP and MEP subsets are isolatable within the hCD34+hCD38+ fraction in both the bone marrow and cord blood (Manz et al., 2002). All are negative for the early lymphoid markers hCD10, hCD7 or hIL-7Rα. These myeloerythroid progenitors are prospectively isolatable according to the expression of hCD45RA and hIL-3Rα. hCD45RA-hIL-3Rαlo (CMPs), hCD45RA+hIL-3Rαlo (GMPs) and hCD45RA-hIL-3Rα- (MEPs) efficiently formed distinct myelo-erythroid colony types according to their definitions. CMPs give rise to MEPs and GMPs in vitro, and a significant proportion of CMPs possess clonal GM and MegE potentials (Manz et al., 2002). Thus, the hierarchical myeloid progenitor relationships demonstrated in mice is well preserved in human hematopoiesis. Phenotypic comparisons between mouse and human subsets show that CD34, a marker positive for only murine CMPs and GMPs, is uniformly expressed on all three human subsets, and that the FcγRII/III (CD16/CD32), marking murine CMPs and GMPs, was not detectable in none of human myeloid progenitors (Manz et al., 2002).

All of these hematolymphoid progenitors develop from hCD34+hCD38- HSC population (Ishikawa et al., 2005), but themselves have no self-renewal activity in xenogeneic transplantation models (Ishikawa et al., 2007), indicating that they are downstream of human LT-HSCs in both the bone marrow and the cord blood.

[page 6693]

The significant difference of Flt3 distribution in human and mouse hematopoiesis suggests that the critical role of Flt3 signaling in hematopoietic development could also be different.


Galy A, Travis M, Cen D, Chen B. (1995). Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. Immunity 3: 459–473.

Hao QL, Zhu J, Price MA, Payne KJ, Barsky LW, Crooks GM. (2001). Identification of a novel, human multilymphoid progenitor in cord blood. Blood 97: 3683–3690.

Ishikawa F, Niiro H, Iino T, Yoshida S, Saito N, Onohara S et al. (2007). The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways. Blood (in press).

Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G et al. (2005). Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood 106: 1565–1573.

Manz MG, Miyamoto T, Akashi K, Weissman IL. (2002). Prospective isolation of human clonogenic common myeloid progenitors. Proc Natl Acad Sci USA 99: 11872–11877.

Anmerkungen

The source is not mentioned at all.

Note that the reference "(Manz et al., 2002)" is atypical here as typically a reference would refer by a number to the bibliography, without giving the author's name in the main body of text.

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