Dhx15 regulates zebrafish definitive hematopoiesis through the unfolded protein response pathway
- Cai, Y., Wang, J., Jin, D., Liu, Q., Xianglei, C., Lili, P., Yang, L., Wang, X., Qian, F., Wang, J., Zhong, T.P., Wang, S.
- Cancer science 112(9): 3884-3894 (Journal)
- Registered Authors
- Jin, Daqing, Zhong, Tao P.
- AML, DEAH box helicase 15, hematopoiesis, unfolded protein response, zebrafish
- MeSH Terms
- Animals, Genetically Modified
- Cell Proliferation/genetics
- DEAD-box RNA Helicases/genetics
- DEAD-box RNA Helicases/metabolism*
- Gene Knockout Techniques
- Hematopoietic Stem Cells/metabolism
- In Situ Hybridization
- Leukemia, Myeloid, Acute/genetics*
- Leukemia, Myeloid, Acute/metabolism
- RNA Helicases/genetics
- RNA Helicases/metabolism
- Unfolded Protein Response/genetics*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- 34077586 Full text @ Cancer Sci.
Cai, Y., Wang, J., Jin, D., Liu, Q., Xianglei, C., Lili, P., Yang, L., Wang, X., Qian, F., Wang, J., Zhong, T.P., Wang, S. (2021) Dhx15 regulates zebrafish definitive hematopoiesis through the unfolded protein response pathway. Cancer science. 112(9):3884-3894.
Gene alterations is recognized as an important event in AML progression. Studies on hematopoiesis of altered genes contribute to a better understanding on their roles in AML progression. Our previous work reported a DEAH box helicase 15 (DHX15) R222G mutation in AML patients, and we showed DHX15 overexpression is associated with poor prognosis in AML patients. In this work, we further study the role of dhx15 in zebrafish developmental hematopoiesis by generating dhx15-/- zebrafish using transcription activator-like effector nuclease technology. Whole-mount in situ hybridization analysis showed hematopoietic stem/progenitor cells are dramatically perturbed when dhx15 were deleted. Immunofluorescence staining indicated inhibited HSPC proliferation instead of accelerated apoptosis were detected in dhx15-/- zebrafish. Furthermore, our data showed HSPC defect is mediated through the unfolded protein response pathway. DHX15 R222G mutation, a recurrent mutation identified in AML patients, displayed a compromised function in restoring HSPCs failure in dhx15-/- ; Tg (hsp: DHX15 R222G) zebrafish. Collectively, this work demonstrated a vital role of dhx15 in the maintenance of definitive hematopoiesis in zebrafish through UPR pathway, and the study of DHX15 and DHX15 R222G mutation may hold clinical significance for evaluating prognosis of AML patients with aberrant DHX15 expression.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes