2. Academic Validation
  3. Targeting JNK pathway promotes human hematopoietic stem cell expansion

Targeting JNK pathway promotes human hematopoietic stem cell expansion

  • Cell Discov. 2019 Jan 8;5:2. doi: 10.1038/s41421-018-0072-8.
Xiong Xiao 1,  Weifeng Lai 2 3,  Huangfan Xie 2 3,  Yang Liu 1,  Weijie Guo 2 3,  Yifang Liu 4,  Yu Li 2 3,  Yuanjun Li 2 3,  Jingliang Zhang 2 3,  Wenhan Chen 2 3,  Minhui Shi 2 3,  Lijun Shang 2 3,  Ming Yin 5,  Chengyan Wang 2 3,  Hongkui Deng 1 2 3
Affiliations

Affiliations

  • 1 1State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology & Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, 518055 China.
  • 2 2The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871 China.
  • 3 3Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Center for Molecular and Translational Medicine, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191 China.
  • 4 4Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, Beijing, 100084 China.
  • 5 Beijing Vitalstar Biotechnology, Beijing, 100012 China.
PMID: 30622738 DOI: 10.1038/s41421-018-0072-8
Abstract

The limited number of human hematopoietic stem cells (HSCs) has restrained their widespread clinical application. Despite great efforts in recent years, the in vitro expansion of HSCs remains a challenge due to incomplete understanding of the signaling networks underlying HSC self-renewal. Here, we show that culturing human cord blood (CB) CD34+ cells with JNK-IN-8, an inhibitor of the JNK signaling pathway, can enhance the self-renewal of HSCs with a 3.88-fold increase in cell number. These cultured CD34+ cells repopulated recipient mice for 21 weeks and can form secondary engraftment that lasted for more than 21 weeks. Knockdown of c-Jun, a major downstream target in the JNK pathway, promoted the expansion of hematopoietic stem and progenitor cells (HSPCs). Our findings demonstrate a critical role of the JNK pathway in regulating HSC expansion, provide new insights into HSC self-renewal mechanism, and may lead to improved clinical application of HSCs.

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