Corbel Catherine, Salaün Josselyne
Institut d'Embryologie Cellulaire et Moléculaire du CNRS, 49 bis, avenue de la Belle Gabrielle, 94736 Nogent-sur-Marne Cedex, France.
Dev Biol. 2002 Mar 15;243(2):301-11. doi: 10.1006/dbio.2001.0553.
Integrin alphaIIb is a cell adhesion molecule expressed in association with beta3 by cells of the megakaryocytic lineage, from committed progenitors to platelets. While it is clear that lymphohemopoietic cells differentiating along other lineages do not express this molecule, it has been questioned whether mammalian hemopoietic stem cells (HSC) and various progenitor cells express it. In this study, we detected alphaIIb expression in midgestation embryo in sites of HSC generation, such as the yolk sac blood islands and the hemopoietic clusters lining the walls of the major arteries, and in sites of HSC migration, such as the fetal liver. Since c-Kit, which plays an essential role in the early stages of hemopoiesis, is expressed by HSC, we studied the expression of the alphaIIb antigen in the c-Kit-positive population from fetal liver and adult bone marrow differentiating in vitro and in vivo into erythromyeloid and lymphocyte lineages. Erythroid and myeloid progenitor activities were found in vitro in the c-Kit(+)alphaIIb(+) cell populations from both origins. On the other hand, a T cell developmental potential has never been considered for c-Kit(+)alphaIIb(+) progenitors, except in the avian model. Using organ cultures of embryonic thymus followed by grafting into athymic nude recipients, we demonstrate herein that populations from murine fetal liver and adult bone marrow contain T lymphocyte progenitors. Migration and maturation of T cells occurred, as shown by the development of both CD4(+)CD8- and CD4-CD8(+) peripheral T cells. Multilineage differentiation, including the B lymphoid lineage, of c-Kit(+)alphaIIb(+) progenitor cells was also shown in vivo in an assay using lethally irradiated congenic recipients. Taken together, these data demonstrate that murine c-Kit(+)alphaIIb(+) progenitor cells have several lineage potentialities since erythroid, myeloid, and lymphoid lineages can be generated.
整合素αIIb是一种细胞黏附分子,由巨核细胞系的细胞(从定向祖细胞到血小板)与β3共同表达。虽然很明显沿着其他谱系分化的淋巴细胞造血细胞不表达这种分子,但哺乳动物造血干细胞(HSC)和各种祖细胞是否表达它一直存在疑问。在本研究中,我们在HSC产生部位(如卵黄囊血岛和大动脉壁内衬的造血簇)以及HSC迁移部位(如胎儿肝脏)的中期妊娠胚胎中检测到了αIIb表达。由于在造血早期起关键作用的c-Kit由HSC表达,我们研究了来自胎儿肝脏和成年骨髓的c-Kit阳性群体中αIIb抗原的表达,这些群体在体外和体内分化为红系和髓系以及淋巴细胞谱系。在来自这两个来源的c-Kit(+)αIIb(+)细胞群体中,体外发现了红系和髓系祖细胞活性。另一方面,除了在鸟类模型中,c-Kit(+)αIIb(+)祖细胞从未被认为具有T细胞发育潜能。通过胚胎胸腺器官培养然后移植到无胸腺裸鼠受体中,我们在此证明来自小鼠胎儿肝脏和成年骨髓的群体含有T淋巴细胞祖细胞。T细胞的迁移和成熟发生了,如CD4(+)CD8-和CD4-CD8(+)外周T细胞的发育所示。在使用致死性照射的同基因受体的实验中,体内也显示了c-Kit(+)αIIb(+)祖细胞的多谱系分化,包括B淋巴细胞谱系。综上所述,这些数据表明小鼠c-Kit(+)αIIb(+)祖细胞具有多种谱系潜能,因为可以产生红系、髓系和淋巴系谱系。