Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors
Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors
复制标题
DOI：
10.1016/j.immuni.2007.02.013
复制
发表时间：
2007-04-01
期刊：
影响因子：
32.4
通讯作者：
Jacobsen, Sten Eirik W.
中科院分区：
文献类型：
--
作者：
Mansson, Robert;Hultquist, Anne;Jacobsen, Sten Eirik W.
最近的研究表明，成年淋巴细胞引发的多能祖细胞（lmpp）具有很少或没有巨核细胞-红细胞潜能，质疑普通髓细胞和淋巴细胞祖细胞作为造血干细胞（HSC）谱系承诺的专门中间体的存在。然而，lmpp的存在仍然存在争议。在此，整体和单细胞分析揭示了转录谱系程序的分层组织，从造血干细胞到lmpp的巨核细胞-红细胞基因下调，持续的粒细胞-单核细胞启动，以及普通淋巴细胞（但不包括B细胞和T细胞特异性）基因上调。这些生物学和分子关系，意味着巨核细胞-红细胞和淋巴细胞通路几乎相互排斥，已经在胎儿造血中建立起来，正如胎儿肝脏中存在lmpp所证明的。lmpp的识别和不同谱系程序的分层有序转录激活和下调与HSC谱系承诺模型相一致，其中从HSC到lmpp，经历不同谱系承诺命运的概率逐渐变化。
Recent studies implicated the existence of adult lymphoid-primed multipotent progenitors (LMPPs) with little or no megakaryocyte-erythroid potential, questioning common myeloid and lymphoid progenitors as obligate intermediates in hematopoietic stem cell (HSC) lineage commitment. However, the existence of LMPPs remains contentious. Herein, global and single-cell analyses revealed a hierarchical organization of transcriptional lineage programs, with downregulation of megakaryocyte-erythroid genes from HSCs to LMPPs, sustained granulocyte-monocyte priming, and upregulation of common lymphoid (but not B and T cell-specific) genes. These biological and molecular relationships, implicating almost mutual exclusion of megakaryocyte-erythroid and lymphoid pathways, are established already in fetal hematopoiesis, as evidenced by existence of LMPPs in fetal liver. The identification of LMPPs and hierarchically ordered transcriptional activation and downregulation of distinct lineage programs is compatible with a model for HSC lineage commitment in which the probability for undergoing different lineage commitment fates changes gradually when progressing from HSCs to LMPPs.