Hematopoietic progenitor/stem cells immortalized by Lhx2 generate functional hematopoietic cells in vivo
Hematopoietic progenitor/stem cells immortalized by Lhx2 generate functional hematopoietic cells in vivo
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DOI：
10.1182/blood.v99.11.3939
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发表时间：
2002-06-01
期刊：
影响因子：
20.3
通讯作者：
Carlsson, L
中科院分区：
文献类型：
--
作者：
do O, PP;Carlsson, L
造血干细胞（HSC）在移植到免疫功能低下的宿主后维持血液形成的能力是独特的。因此，HSC在体外的扩增对于许多临床应用是重要的，但由于调节自我更新过程的机制定义不清，因此成功有限。我们以前已经表明，LIM同源框基因Lhx2的表达在造血祖细胞衍生自胚胎干细胞体外分化产生永生化的多能造血祖细胞系。然而，早期胚胎来源的HSC，包括来自分化的胚胎干细胞的那些，在移植后移植成人受体时是低效的。为了解决Lhx2是否可以使可以植入成年受体的造血祖细胞/干细胞永生化，我们在源自成人骨髓的造血祖细胞/干细胞中表达Lhx2。这种方法允许产生永生化的生长因子依赖性造血祖细胞/干细胞系，其在移植到致死性照射的小鼠中后可以产生红系、髓系和淋巴样细胞。当移植到干细胞缺陷小鼠中时，这些细胞系可以在初级、次级和三级受体中产生显著比例的循环红细胞至少18个月。因此，Lhx2使多能造血祖细胞/干细胞永生化，所述多能造血祖细胞/干细胞可以在移植到致死性照射的宿主中后产生功能性后代，并且可以长期重新填充干细胞缺陷的宿主。(C)2002年，美国血液学会。
Hematopoietic stem cells (HSCs) are unique in their capacity to maintain blood formation following transplantation into immunocompromised hosts. Expansion of HSCs in vitro is therefore important for many clinical applications but has met with limited success because the mechanisms regulating the self-renewal process are poorly defined. We have previously shown that expression of the LIM-homeobox gene Lhx2 in hematopoietic progenitor cells derived from embryonic stem cells differentiated in vitro generates immortalized multipotent hematopoietic progenitor cell lines. However, HSCs of early embryonic origin, including those derived from differentiated embryonic stem cells, are inefficient in engrafting adult recipients upon transplantation. To address whether Lhx2 can immortalize hematopoietic progenitor/stem cells that can engraft adult recipients, we expressed Lhx2 in hematopoietic progenitor/stem cells derived from adult bone marrow. This approach allowed for the generation of immortalized growth factor-dependent hematopoietic progenitor/stem cell lines that can generate erythroid, myeloid, and lymphoid cells upon transplantation into lethally irradiated mice. When transplanted into stem cell-deficient mice, these cell lines can generate a significant proportion of circulating erythrocytes in primary, secondary, and tertiary recipients for at least 18 months. Thus, Lhx2 immortalizes multipotent hematopoietic progenitor/stem cells that can generate functional progeny following transplantation into lethally irradiated hosts and can long-term repopulate stem cell-deficient hosts. (C) 2002 by The American Society of Hematology.