Cpeb1b介导的mRNA加尾调控造血干祖细胞发育

众所周知，各种发育相关的信号通路在造血干祖细胞发育中发挥着不同的作用；然而，这些通路是如何受到时空特异性调控的尚不完全清楚。转录后调控通过调节RNA分子的代谢在信号通路特异性调节中起着关键作用。Cpeb1b是一种序列特异性的RNA结合蛋白，属于CPEB家族，这个家族参与调控细胞质中的mRNA多聚腺苷酸化。CPEB家族介导的胞质多聚腺苷酸化涉及多个生物学过程，包括：生殖细胞发育，细胞衰老，炎性反应和神经突触可塑性等。然而，目前尚不清楚CPEB家族介导的胞质多聚腺苷酸化是否通过影响特定信号通路参与调控造血干祖细胞发育。我们未公开的数据表明Cpeb1b缺失会导致斑马鱼造血干祖细胞的产生过程出现缺陷。通过本项目的实施，我们将进一步揭示Cpeb1b介导的细胞质多聚腺苷酸化在造血干祖细胞发育中的作用及机制。这项研究将对转录后调控如何介导发育信号通路的时空特异性，从而准确地执行细胞命运决定提供新的见解。

It is well known that various developmental signals play diverse roles in hematopoietic stem and progenitor cell (HSPC) development; however, how these signaling pathways are spatiotemporally regulated remains incompletely understood. Post-transcriptional regulation plays a crucial role in signaling specificity regulation through regulating RNA molecules metabolism. Cpeb1b (cytoplasmic polyadenylation element-binding 1b) is a sequence-specific RNA binding protein that belongs to the CPEB family, which is thought to regulate cytoplasmic polyadenylation. Cytoplasmic polyadenylation regulated by CPEB family is involved in diverse biological processes including germ cell development, cellular senescence, inflammatory immune response and neuronal synaptic plasticity. However, it remains unknown whether and how CPEB-mediated cytoplasmic polyadenylation is involved in HSPC development regulation. Our previous unpublished data show that Cpeb1b deficiency can lead to defects in zebrafish HSPC production. In this grant application, we plan to uncover the role of Cpeb1b-mediated cytoplasmic polyadenylation in HSPC development. This study may provide new insights into how signals are spatiotemporally regulated by post-transcriptional regulation to accurately execute cell fate decision in HSPC development.