2. Academic Validation
  3. Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

  • Protein Cell. 2023 May 9;pwad027. doi: 10.1093/procel/pwad027.
Jinghui Lei 1 2,  Xiaoyu Jiang 3 4,  Daoyuan Huang 1 2,  Ying Jing 1 2,  Shanshan Yang 1 2,  Lingling Geng 1 2,  Yupeng Yan 3 5,  Fangshuo Zheng 6,  Fang Cheng 4 7,  Weiqi Zhang 4 5 8 9 10 11 12,  Juan Carlos Izpisua Belmonte 13,  Guang-Hui Liu 1 3 4 5 14 12,  Si Wang 1 2 6 12,  Jing Qu 15 4 5 14 12
Affiliations

Affiliations

  • 1 Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China.
  • 2 Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
  • 3 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  • 4 University of Chinese Academy of Sciences, Beijing 100049, China.
  • 5 Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China.
  • 6 The Fifth People's Hospital of Chongqing, Chongqing 400062, China.
  • 7 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Beijing 100101, Chinese.
  • 8 CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
  • 9 China National Center for Bioinformation, Beijing 100101, China.
  • 10 Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China.
  • 11 Sino-Danish Center for Education and Research, Beijing 101408, China.
  • 12 Aging Biomarker Consortium, China.
  • 13 Altos Labs, San Diego, CA, 92121, USA.
  • 14 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • 15 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
PMID: 37158785 DOI: 10.1093/procel/pwad027
Abstract

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cells types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells (hESCs) and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

Keywords

HIF-1; human ESC; regeneration; vascular cell.

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