Ng Samuel Yao-Ming, Yoshida Toshimi, Zhang Jiangwen, Georgopoulos Katia
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Immunity. 2009 Apr 17;30(4):493-507. doi: 10.1016/j.immuni.2009.01.014. Epub 2009 Apr 2.
The mechanisms regulating lineage potential during early hematopoiesis were investigated. First, a cascade of lineage-affiliated gene expression signatures, primed in hematopoietic stem cells (HSCs) and differentially propagated in lineage-restricted progenitors, was identified. Lymphoid transcripts were primed as early as the HSC, together with myeloid and erythroid transcripts. Although this multilineage priming was resolved upon subsequent lineage restrictions, an unexpected cosegregation of lymphoid and myeloid gene expression and potential past a nominal myeloid restriction point was identified. Finally, we demonstrated that whereas the zinc finger DNA-binding factor Ikaros was required for induction of lymphoid lineage priming in the HSC, it was also necessary for repression of genetic programs compatible with self-renewal and multipotency downstream of the HSC. Taken together, our studies provide new insight into the priming and restriction of lineage potentials during early hematopoiesis and identify Ikaros as a key bivalent regulator of this process.
研究了早期造血过程中调节谱系潜能的机制。首先,鉴定了一系列在造血干细胞(HSC)中启动并在谱系受限祖细胞中差异传播的谱系相关基因表达特征。淋巴样转录本早在HSC阶段就与髓样和红系转录本一起启动。尽管这种多谱系启动在随后的谱系限制时得到解决,但发现淋巴样和髓样基因表达及潜能在超过名义上的髓样限制点后意外地共同分离。最后,我们证明,锌指DNA结合因子Ikaros对于在HSC中诱导淋巴样谱系启动是必需的,对于抑制与HSC下游自我更新和多能性相容的遗传程序也是必需的。综上所述,我们的研究为早期造血过程中谱系潜能的启动和限制提供了新的见解,并将Ikaros确定为这一过程的关键双价调节因子。
Curr Opin Immunol. 2010-3-17
Nat Immunol. 2006-4
J Immunol. 2003-3-15
Int J Hematol. 2014-9
Nat Chem Biol. 2025-5-26
Adv Exp Med Biol. 2024
Front Oncol. 2024-6-24
Biomedicines. 2024-1-1
J Leukoc Biol. 2024-6-28
N Engl J Med. 2009-1-29
N Engl J Med. 2009-1-29
Immunity. 2008-8-15
Immunity. 2008-8-15
Nature. 2008-4-10