Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity
Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity
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DOI：
10.1182/blood-2009-08-236398
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发表时间：
2010-04-01
期刊：
影响因子：
20.3
通讯作者：
Sigvardsson, Mikael
中科院分区：
文献类型：
--
作者：
Mansson, Robert;Zandi, Sasan;Sigvardsson, Mikael
为了研究参与调节淋巴谱系定型的分子事件，我们将λ 5报告基因转基因小鼠与Rag 1-GFP敲入小鼠杂交。这使我们能够将普通淋巴祖细胞和前原B（A级分）细胞亚破碎成λ 5（-）Rag 1（低）、λ 5（-）Rag 1（高）和λ 5（+）Rag 1（高）细胞。克隆体外分化分析表明，Rag 1（低）细胞产生B/T和NK细胞。Rag 1（高）细胞显示NK细胞潜能降低，但保留产生B和T谱系细胞的能力，而λ 5（+）细胞则是B谱系受限的。Ebf 1和Pax 5的表达主要局限于Rag 1（高）人群。这些细胞还表达了更高水平的表面蛋白LY 6D，为分析早期淋巴发育提供了额外的工具。这些数据表明，经典的共同淋巴祖细胞室组成的混合物的细胞相对有限的谱系潜力，从而打开新的可能性，调查早期造血。（血。2010;115（13）：2601-2609）
To investigate molecular events involved in the regulation of lymphoid lineage commitment, we crossed lambda 5 reporter transgenic mice to Rag1-GFP knockin mice. This allowed us to subfractionate common lymphoid progenitors and pre-pro-B (fraction A) cells into lambda 5(-)Rag1(low), lambda 5(-)Rag1(high), and lambda 5(+)Rag1(high) cells. Clonal in vitro differentiation analysis demonstrated that Rag1(low) cells gave rise to B/T and NK cells. Rag1(high) cells displayed reduced NK-cell potential with preserved capacity to generate B- and T-lineage cells, whereas the lambda 5(+) cells were B-lineage restricted. Ebf1 and Pax5 expression was largely confined to the Rag1(high) populations. These cells also expressed a higher level of the surface protein LY6D, providing an additional tool for the analysis of early lymphoid development. These data suggest that the classic common lymphoid progenitor compartment composes a mixture of cells with relatively restricted lineage potentials, thus opening new possibilities to investigate early hematopoiesis. (Blood. 2010;115(13):2601-2609)