Activation of OCT4 enhances ex vivo expansion of human cord blood hematopoietic stem and progenitor cells by regulating HOXB4 expression. Huang X, Lee MR, Cooper S, Hangoc G, Hong KS, Chung HM, Broxmeyer HE. Leukemia. 2015 Jul 23. doi: 10.1038/leu.2015.189.

Speaker: Tan Sia Seng (陳聲昇)                                   Time: 13:00~14:00, Dec. 16, 2015

Commentator: Ai-Li Shiau, Ph.D. (蕭璦莉 教授)       Place: Room 601

Abstract:

Hematopoietic stem cells (HSC) known as a stem cell subset which involve in producing the members of peripheral blood cells via process of hematopoiesis. HSC have an important characteristic which is self-renewal that can maintain the properties of HSC. Octamer-binding protein 4 (OCT4) is one of the critical proteins, involving in self-renewal process. In previous studies, a small molecule called Oct4-activating compound 1 (OAC1) could enhance expression of Oct4 in embryonic stem cell (1). OAC1 treated human cord blood (CB) which is used as the source of HSC found that OAC1 treatment resulted in 7.6 fold increase in the number of CD34⁺ HSC compare to untreated CD34⁺. However, another important transcription factor HOXB4, an essential regulator for HSC self-renewal characteristic and also can be a marker of primitive HSC (2), activated by Oct4 after binding to HOXB4 promoter site. HSC expanded ex vivo with OAC1 treatment could form different colony assayed by colony forming unit (CFU) method, suggesting expanded HSC still had a potential to differentiate further to hematopoietic progenitor cell. HSC from humantransplanted into irradiated NSG mice revealed that OAC1 treated CD34⁺ cell, whether in short term or long term engrafting HSC, significantly increased in SCID repopulating cell (SRC) compared with untreated CD34⁺. Transplanted OAC1-mediated HSC didn’t induce malignant transformation in both primary and secondary transplantations during observed periods, indicating a potential advantage for clinical HSC transplantation.

References:

1.    Li W, Tian E, Chen ZX, Sun G, Ye P, Yang S, et al. Identification of Oct4-activating compounds that enhance reprogramming efficiency. Proc Natl Acad Sci U S A. 2012;109(51):20853-8.

2.    Forrester LM, Jackson M. Mechanism of action of HOXB4 on the hematopoietic differentiation of embryonic stem cells. Stem Cells. 2012;30(3):379-85.