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造血干细胞缺陷型胚胎中存在功能性 B-1 祖细胞,其发育依赖于 Cbfβ。

Functional B-1 progenitor cells are present in the hematopoietic stem cell-deficient embryo and depend on Cbfβ for their development.

机构信息

Department of Pediatrics, Wells Center for Pediatric Research and.

Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences-Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama 230-0045, Japan.

出版信息

Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12151-6. doi: 10.1073/pnas.1407370111. Epub 2014 Aug 4.

Abstract

The fetal liver is a major hematopoietic site containing progenitor cells that give rise to nearly all blood cells, including B-1 cells. Because the fetal liver is not a de novo site of hematopoietic stem cell (HSC) or progenitor-cell emergence, it must be seeded by yolk sac (YS)-derived erythromyeloid progenitors at embryonic day (E) 8.5-E10 and aorta-gonado-mesonephros (AGM)-derived HSCs at E10.5-E11.5. Although the B-1 progenitor cell pool in the fetal liver is considered to be of HSC origin, we have previously proposed that YS-derived B-1 progenitors may also contribute to this pool. Until now, it has been impossible to determine whether HSC-independent B-1 progenitor cells exist in the fetal liver. Here, we demonstrate the presence of transplantable fetal-liver B-1 and marginal zone B progenitor cells in genetically engineered HSC-deficient embryos. HSC-deficient YS and AGM tissues produce B-1 progenitors in vitro and thus may serve as sites of origin for the B-1 progenitors that seed the fetal liver. Furthermore, we have found that core-binding factor beta (Cbfβ) expression is required for fetal-liver B-1 progenitor cell maturation and expansion. Our data provide, to our knowledge, the first evidence for the presence of B-1 progenitor cells in the fetal liver that arise independently of HSCs and implicate Cbfβ as a critical molecule in the development of this lineage.

摘要

胎儿肝脏是一个主要的造血部位,其中包含祖细胞,这些祖细胞可以产生几乎所有的血细胞,包括 B-1 细胞。由于胎儿肝脏不是造血干细胞(HSC)或祖细胞出现的新部位,它必须在胚胎第 8.5 天至第 10 天由卵黄囊(YS)衍生的红髓髓系祖细胞和第 10.5 天至第 11.5 天的主动脉性腺中肾(AGM)衍生的 HSCs 播种。虽然胎儿肝脏中的 B-1 祖细胞池被认为是 HSC 起源的,但我们之前提出,YS 衍生的 B-1 祖细胞也可能对此池做出贡献。到目前为止,还不可能确定胎儿肝脏中是否存在独立于 HSC 的 B-1 祖细胞。在这里,我们证明了在基因工程 HSC 缺陷型胚胎中存在可移植的胎儿肝脏 B-1 和边缘区 B 祖细胞。HSC 缺陷型 YS 和 AGM 组织在体外产生 B-1 祖细胞,因此可能是播种胎儿肝脏的 B-1 祖细胞的起源部位。此外,我们发现核心结合因子β(Cbfβ)的表达对于胎儿肝脏 B-1 祖细胞的成熟和扩增是必需的。我们的数据提供了,据我们所知,在 HSCs 独立的情况下,胎儿肝脏中存在 B-1 祖细胞的第一个证据,并暗示 Cbfβ 是该谱系发育的关键分子。

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