Journal article
P. Ernst, D. Bryder, Kenneth L. Jones, Devon Trahan, Weiwei Yang
Experimental Hematology, 2019
Experimental Hematology, 2019
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APA
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Ernst, P., Bryder, D., Jones, K. L., Trahan, D., & Yang, W. (2019). AN MLL1-REGULATED RAC/RHO/INTEGRIN SIGNALING AXIS ENHANCES HEMATOPOIESIS FROM EMBRYONIC HEMOGENIC ENDOTHELIAL PRECURSORS. Experimental Hematology.
Chicago/Turabian
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Ernst, P., D. Bryder, Kenneth L. Jones, Devon Trahan, and Weiwei Yang. “AN MLL1-REGULATED RAC/RHO/INTEGRIN SIGNALING AXIS ENHANCES HEMATOPOIESIS FROM EMBRYONIC HEMOGENIC ENDOTHELIAL PRECURSORS.” Experimental Hematology (2019).
MLA
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Ernst, P., et al. “AN MLL1-REGULATED RAC/RHO/INTEGRIN SIGNALING AXIS ENHANCES HEMATOPOIESIS FROM EMBRYONIC HEMOGENIC ENDOTHELIAL PRECURSORS.” Experimental Hematology, 2019.
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@article{p2019a,
title = {AN MLL1-REGULATED RAC/RHO/INTEGRIN SIGNALING AXIS ENHANCES HEMATOPOIESIS FROM EMBRYONIC HEMOGENIC ENDOTHELIAL PRECURSORS},
year = {2019},
journal = {Experimental Hematology},
author = {Ernst, P. and Bryder, D. and Jones, Kenneth L. and Trahan, Devon and Yang, Weiwei}
}
Abstract
We have previously shown that the Mixed Lineage Leukemia (MLL1, KMT2A) gene is critical for the development and maintenance of transplantable hematopoietic stem cells (HSCs), however, whether overexpression of wild-type (WT) MLL1 could enhance HSC production has not been tested due to lack of suitable model systems. Here, we report the WT MLL1 inducible embryonic stem (ES) cell model and show that induction of MLL1 during ES differentiation selectively expands hematopoietic colony potential from a transitional c-Kit+/CD41+ population. Single cell sequencing analysis illustrates the inherent heterogeneity of this population and demonstrates that MLL1 induction shifts its composition from a hemogenic endothelium identity toward multilineage hematopoietic identities. Surprisingly, this does not occur through increasing Hox or other canonical MLL1 target genes, but occurs through an enhanced Rac/Rho/integrin signaling state, which increases responsiveness to VLA4 ligands and enhances hematopoietic commitment. Together, our data implicate a Rac/Rho/integrin signaling axis as critical during the endothelial to hematopoietic transition and demonstrate that WT MLL1 actives this axis.