Hydrogel-based microenvironment engineering of haematopoietic stem cells

Zhu, Meng; Wang, Qiwei; Gu, Tianning; Han, Yingli; Zeng, Xin; Li, Jinxin; Dong, Jian; Huang, He; Qian, Pengxu

doi:10.1007/s00018-023-04696-w

Cited by 2 publications

(1 citation statement)

References 180 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The STAT3 signal plays a central role in inducing myeloid differentiation in response to growth factors [ 29 – 32 ]. Our findings provide substantiation for the role of PRTN3 in identifying cleavage sites on STAT3, resulting in ubiquitin-mediated degradation and subsequent reduction in STAT3-dependent gene expression.…”

Section: Discussionmentioning

confidence: 99%

Proteinase 3 depletion attenuates leukemia by promoting myeloid differentiation

Liu,

Sun,

Zhao

et al. 2024

Cell Death Differ

View full text Add to dashboard Cite

Hematopoietic stem and progenitor cells (HSPCs) that have impaired differentiation can transform into leukemic blasts. However, the mechanism that controls differentiation remains elusive. Here, we show that the genetic elimination of Proteinase 3 (PRTN3) in mice led to spontaneous myeloid differentiation. Mechanistically, our findings indicate that PRTN3 interacts with the N-terminal of STAT3, serving as a negative regulator of STAT3-dependent myeloid differentiation. Specifically, PRTN3 promotes STAT3 ubiquitination and degradation, while simultaneously reducing STAT3 phosphorylation and nuclear translocation during G-CSF-stimulated myeloid differentiation. Strikingly, pharmacological inhibition of STAT3 (Stattic) partially counteracted the effects of PRTN3 deficiency on myeloid differentiation. Moreover, the deficiency of PRTN3 in primary AML blasts promotes the differentiation of those cells into functional neutrophils capable of chemotaxis and phagocytosis, ultimately resulting in improved overall survival rates for recipients. These findings indicate PRTN3 exerts an inhibitory effect on STAT3-dependent myeloid differentiation and could be a promising therapeutic target for the treatment of acute myeloid leukemia.

show abstract

Section: Discussionmentioning

confidence: 99%