定义调节干细胞维持、增殖和分化的机制对于确定改善压力下干细胞功能的疗法至关重要。在这里，我们确定了肿瘤抑制因子，生长抑制剂 4 (Ing4)，作为造血干细胞 (HSC) 稳态的关键调节因子。 Ing4 缺陷的癌细胞系模型表明，Ing4 具有肿瘤抑制因子的功能，部分原因是 Ing4 介导的几个主要信号通路（包括 c-Myc）的调节。在 HSC 中，我们发现 Ing4 缺陷会促进与激活相关的基因表达特征，但 HSC 却停滞在 G0 期，表达多种静止标记。从功能上来说，Ing4 缺陷的 HSC 在移植后表现出强大的再生能力。我们的研究结果表明，Ing4 缺陷会促进 HSC 的平衡状态，在这种状态下，它们在转录上似乎已准备好激活，但仍处于静止状态。我们的模型为进一步识别和表征 HSC 中控制静止和自我更新的途径提供了关键工具。© 2024 作者。

Defining the mechanisms that regulate stem cell maintenance, proliferation, and differentiation is critical for identifying therapies for improving stem cell function under stress. Here, we have identified the tumor suppressor, inhibitor of growth 4 (Ing4), as a critical regulator of hematopoietic stem cell (HSC) homeostasis. Cancer cell line models with Ing4 deficiency have shown that Ing4 functions as a tumor suppressor, in part, due to Ing4-mediated regulation of several major signaling pathways, including c-Myc. In HSCs, we show Ing4 deficiency promotes gene expression signatures associated with activation, yet HSCs are arrested in G0, expressing several markers of quiescence. Functionally, Ing4-deficient HSCs demonstrate robust regenerative capacity following transplantation. Our findings suggest Ing4 deficiency promotes a poised state in HSCs, where they appear transcriptionally primed for activation but remain in a resting state. Our model provides key tools for further identification and characterization of pathways that control quiescence and self-renewal in HSCs.© 2024 The Authors.