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A gap-junction-mediated, calcium-signaling network controls blood progenitor fate decisions in hematopoiesis
Current Biology ( IF 8.1 ) Pub Date : 2021-09-03 , DOI: 10.1016/j.cub.2021.08.027
Kevin Y L Ho 1 , Rohan J Khadilkar 2 , Rosalyn L Carr 3 , Guy Tanentzapf 1
Affiliation  

Stem cell homeostasis requires coordinated fate decisions among stem cells that are often widely distributed within a tissue at varying distances from their stem cell niche. This requires a mechanism to ensure robust fate decisions within a population of stem cells. Here, we show that, in the Drosophila hematopoietic organ, the lymph gland (LG), gap junctions form a network that coordinates fate decisions between blood progenitors. Using live imaging of calcium signaling in intact LGs, we find that blood progenitors are connected through a signaling network. Blocking gap junction function disrupts this network, alters the pattern of encoded calcium signals, and leads to loss of progenitors and precocious blood cell differentiation. Ectopic and uniform activation of the calcium-signaling mediator CaMKII restores progenitor homeostasis when gap junctions are disrupted. Overall, these data show that gap junctions equilibrate cell signals between blood progenitors to coordinate fate decisions and maintain hematopoietic homeostasis.



中文翻译:

间隙连接介导的钙信号网络控制造血过程中的血祖细胞命运决定

干细胞稳态需要干细胞之间协调的命运决定,这些干细胞通常广泛分布在距其干细胞生态位不同距离的组织内。这需要一种机制来确保在干细胞群体中做出稳健的命运决定。在这里,我们表明,在果蝇造血器官、淋巴腺 (LG)、间隙连接形成一个网络,协调血液祖细胞之间的命运决定。使用完整 LG 中钙信号的实时成像,我们发现血液祖细胞通过信号网络连接。阻断间隙连接功能会破坏该网络,改变编码钙信号的模式,并导致祖细胞丧失和早熟血细胞分化。当间隙连接被破坏时,钙信号介质 CaMKII 的异位和均匀激活可恢复祖细胞的稳态。总体而言,这些数据表明间隙连接平衡了血液祖细胞之间的细胞信号,以协调命运决定并维持造血稳态。

更新日期:2021-11-08
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