Månsson Robert, Hultquist Anne, Luc Sidinh, Yang Liping, Anderson Kristina, Kharazi Shabnam, Al-Hashmi Suleiman, Liuba Karina, Thorén Lina, Adolfsson Jörgen, Buza-Vidas Natalija, Qian Hong, Soneji Shamit, Enver Tariq, Sigvardsson Mikael, Jacobsen Sten Eirik W
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, 221 84 Lund, Sweden.
Immunity. 2007 Apr;26(4):407-19. doi: 10.1016/j.immuni.2007.02.013. Epub 2007 Apr 12.
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.
近期研究表明存在成年淋巴样启动多能祖细胞（LMPP），其巨核细胞-红系潜能很小或没有，这对常见髓系和淋巴系祖细胞作为造血干细胞（HSC）谱系定向中的必然中间体提出了质疑。然而，LMPP的存在仍存在争议。在此，全局和单细胞分析揭示了转录谱系程序的分层组织，从HSC到LMPP，巨核细胞-红系基因下调，粒细胞-单核细胞启动持续存在，以及常见淋巴系（而非B和T细胞特异性）基因上调。这些生物学和分子关系表明巨核细胞-红系和淋巴系途径几乎相互排斥，这在胎儿造血过程中就已确立，胎儿肝脏中存在LMPP就证明了这一点。LMPP的鉴定以及不同谱系程序的分层有序转录激活和下调与HSC谱系定向模型相符，在该模型中，从HSC发展到LMPP时，经历不同谱系定向命运的概率会逐渐变化。
