2. Academic Validation
  3. BF170 hydrochloride enhances the emergence of hematopoietic stem and progenitor cells

BF170 hydrochloride enhances the emergence of hematopoietic stem and progenitor cells

  • Development. 2024 Jul 1;151(13):dev202476. doi: 10.1242/dev.202476.
WenYe Liu 1,  YuYan Ding 1,  Zheng Shen 1,  Cong Xu 2,  William Yi 2,  Ding Wang 3,  Yi Zhou 2,  Leonard I Zon 2 4,  Jing-Xia Liu 1
Affiliations

Affiliations

  • 1 College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
  • 2 Stem Cell Program and Hematology/Oncology, Children's Hospital and Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
  • 3 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
  • 4 Howard Hughes Medical Institute/Children's Hospital, 300 Longwood Avenue, Karp 8, Boston, MA 02115, USA.
PMID: 38940293 DOI: 10.1242/dev.202476
Abstract

Generation of hematopoietic stem and progenitor cells (HSPCs) ex vivo and in vivo, especially the generation of safe therapeutic HSPCs, still remains inefficient. In this study, we have identified compound BF170 hydrochloride as a previously unreported pro-hematopoiesis molecule, using the differentiation assays of primary zebrafish blastomere Cell Culture and mouse embryoid bodies (EBs), and we demonstrate that BF170 hydrochloride promoted definitive hematopoiesis in vivo. During zebrafish definitive hematopoiesis, BF170 hydrochloride increases blood flow, expands hemogenic endothelium (HE) cells and promotes HSPC emergence. Mechanistically, the primary cilia-Ca2+-Notch/NO signaling pathway, which is downstream of the blood flow, mediated the effects of BF170 hydrochloride on HSPC induction in vivo. Our findings, for the first time, reveal that BF170 hydrochloride is a compound that enhances HSPC induction and may be applied to the ex vivo expansion of HSPCs.

Keywords

BF170 hydrochloride; Blood flow; Ca2+; HSPCs; Notch/NO; Primary cilia.

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