The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment.
The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment.
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DOI：
10.1038/ni.2615
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发表时间：
2013-07
影响因子：
30.5
通讯作者：
Dick JE
中科院分区：
文献类型：
--
作者：
Laurenti E;Doulatov S;Zandi S;Plumb I;Chen J;April C;Fan JB;Dick JE
了解分化程序如何从造血干细胞（HSC）的基因表达图谱中产生，对于开发新的临床疗法至关重要。我们通过追踪人类造血干细胞和8种早期祖细胞群的转录组变化，绘制了细胞定向分化最初步骤的转录动态图谱。转录程序广泛共享，跨越谱系潜能边界，且并非严格地与特定谱系相关。干细胞、淋巴系和髓系程序的要素保留在多淋巴祖细胞（MLP）中，反映出一种混合转录状态。基于功能性单细胞分析，BCL11A、SOX4和TEAD1调控多淋巴祖细胞内的转录网络，导致B细胞特化。总体而言，我们表明整合的转录组方法能够识别多能性的新型调控因子，并揭示淋巴系定向分化中额外的复杂性。
Understanding how differentiation programs originate from within the gene expression landscape of hematopoietic stem cells (HSC) is crucial to develop new clinical therapies. We mapped the transcriptional dynamics underlying the first steps of commitment by tracking transcriptome changes in human HSC and eight early progenitor populations. Transcriptional programs are extensively shared, extend across lineage-potential boundaries, and are not strictly lineage-affiliated. Elements of stem, lymphoid and myeloid programs are retained in multi-lymphoid progenitors (MLP), reflecting a hybrid transcriptional state. Based on functional single cell analysis, BCL11A, SOX4 and TEAD1 governed transcriptional networks within MLPs, leading to B cell specification. Overall, we show that integrated transcriptome approaches can identify novel regulators of multipotency and uncover additional complexity in lymphoid commitment.