Unknown

Dataset Information

0

MSX2 suppression through inhibition of TGF? signaling enhances hematopoietic differentiation of human embryonic stem cells.


ABSTRACT: BACKGROUND:Strategies of generating functional blood cells from human pluripotent stem cells (hPSCs) remain largely unsuccessful due to the lack of a comprehensive understanding of hematopoietic development. Endothelial-to-hematopoietic transition (EHT) serves as the pivotal mechanism for the onset of hematopoiesis and is negatively regulated by TGF-? signaling. However, little is known about the underlying details of TGF-? signaling during EHT. METHODS:In this study, by applying genome-wide gene profiling, we identified muscle segment homeobox2 (MSX2) as a potential mediator of TGF-? signaling during EHT. We generated MSX2-deleted human embryonic stem cell (hESC) lines using the CRISPR/Cas9 technology and induced them to undergo hematopoietic differentiation. The role of MSX2 in hematopoiesis and functional regulation of TGF? signaling in EHT was studied. RESULTS:We identified MSX2 as a novel regulator of human hematopoiesis. MSX2 deletion promotes the production of hematopoietic cells from hESCs. Functional and bioinformatics studies further demonstrated that MSX2 deletion augments hematopoietic differentiation of hESCs by facilitating EHT. Mechanistically, MSX2 acts as a downstream target of TGF? signaling to mediate its function during EHT. CONCLUSIONS:Our results not only improve the understanding of EHT, but may also provide novel insight into the efficient production of functional blood cells from hPSCs for regenerative medicine.

SUBMITTER: Wang H 

PROVIDER: S-EPMC7132876 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

MSX2 suppression through inhibition of TGFβ signaling enhances hematopoietic differentiation of human embryonic stem cells.

Wang Hongtao H   Wang Mengge M   Wang Yu Y   Wen Yuqi Y   Chen Xiaoyuan X   Wu Dan D   Su Pei P   Zhou Wen W   Shi Lihong L   Zhou Jiaxi J  

Stem cell research & therapy 20200405 1


<h4>Background</h4>Strategies of generating functional blood cells from human pluripotent stem cells (hPSCs) remain largely unsuccessful due to the lack of a comprehensive understanding of hematopoietic development. Endothelial-to-hematopoietic transition (EHT) serves as the pivotal mechanism for the onset of hematopoiesis and is negatively regulated by TGF-β signaling. However, little is known about the underlying details of TGF-β signaling during EHT.<h4>Methods</h4>In this study, by applying  ...[more]

Similar Datasets

| S-EPMC6010451 | biostudies-literature
| S-EPMC4834039 | biostudies-literature
| S-EPMC4817813 | biostudies-literature
| S-EPMC4464748 | biostudies-literature
| S-EPMC5516306 | biostudies-literature
| S-EPMC3850021 | biostudies-literature
| S-EPMC7814632 | biostudies-literature
| S-EPMC4121367 | biostudies-literature
| S-EPMC9530850 | biostudies-literature
| S-EPMC3471724 | biostudies-literature