International Journal of Hematology

, Volume 107, Issue 3, pp 311–319 | Cite as

Notch1 expression is regulated at the post-transcriptional level by the 3′ untranslated region in hematopoietic stem cell development

  • Shinichi Mizuno
  • Tadafumi Iino
  • Hidetoshi Ozawa
  • Yojiro Arinobu
  • Yong Chong
  • Koichi Akashi
Original Article


In hematopoiesis, the expression of critical genes is regulated in a stage-specific manner to maintain normal hematopoiesis. Notch1 is an essential gene involved in the commitment and development of the T-cell lineage. However, the regulation of Notch1 in hematopoiesis is controversial, particularly at the level of hematopoietic stem cell (HSC). Here, we found that the expression of Notch1 is controlled at the post-transcriptional level in HSCs. HSCs express a considerable level of Notch1 mRNA, but its protein level is very low, suggesting a post-transcriptional suppression for Notch1. Using a retroviral sensor vector expressing a fusion mRNA of GFP and 3′ untranslated region (3′UTR) of a target gene, we demonstrated that the Notch1-3′UTR had a post-translational suppressive effect only at the HSC but not in the downstream progenitor stages. The sequence motif AUnA was required for this post-transcriptional regulation by the Notch1-3′UTR. Interestingly, this Notch1-3′UTR-mediated suppressive effect was relieved when HSCs were placed in the thymus, but not in the bone marrow. Thus, the expression of Notch1 in HSCs is regulated by microenvironment at the post-transcriptional level, which may control T lymphoid lineage commitment from HSCs.


Notch1 3′UTR Post-transcriptional regulation Hematopoietic stem cell 



This work was supported in part by grants from the National Institutes of Health (NIH) (DK050654, DK061320, and CA072009) and by a grant-in-aid for Scientific Research (B) (#22390196) from the Japan Society for the Promotion of Science.

Compliance with ethical standards

Conflict of interest

The authors declared that no conflict of interest exists.


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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  1. 1.Center for Advanced Medical InnovationKyushu UniversityFukuokaJapan
  2. 2.Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical SciencesFukuokaJapan
  3. 3.Center for Cellular and Molecular MedicineKyushu University HospitalFukuokaJapan
  4. 4.Division of Hematology and Oncology, Department of MedicineKurume University School of MedicineFukuokaJapan
  5. 5.Department of Cancer Immunology and AIDsDana-Farber Cancer InstituteBostonUSA

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