Journal article
Weiwei Yang, Weiwei Yang, G. Trahan, Elizabeth D. Howell, N. Speck, Kenneth L. Jones, A. Gillen, K. Riemondy, J. Hesselberth, D. Bryder, D. Bryder, P. Ernst
Stem Cell Reports, 2020
Stem Cell Reports, 2020
Semantic Scholar
DOI
PubMedCentral
PubMed
Cite
Cite
APA
Click to copy
Yang, W., Yang, W., Trahan, G., Howell, E. D., Speck, N., Jones, K. L., … Ernst, P. (2020). Enhancing Hematopoiesis from Murine Embryonic Stem Cells through MLL1-Induced Activation of a Rac/Rho/Integrin Signaling Axis. Stem Cell Reports.
Chicago/Turabian
Click to copy
Yang, Weiwei, Weiwei Yang, G. Trahan, Elizabeth D. Howell, N. Speck, Kenneth L. Jones, A. Gillen, et al. “Enhancing Hematopoiesis from Murine Embryonic Stem Cells through MLL1-Induced Activation of a Rac/Rho/Integrin Signaling Axis.” Stem Cell Reports (2020).
MLA
Click to copy
Yang, Weiwei, et al. “Enhancing Hematopoiesis from Murine Embryonic Stem Cells through MLL1-Induced Activation of a Rac/Rho/Integrin Signaling Axis.” Stem Cell Reports, 2020.
BibTeX Click to copy
@article{weiwei2020a,
title = {Enhancing Hematopoiesis from Murine Embryonic Stem Cells through MLL1-Induced Activation of a Rac/Rho/Integrin Signaling Axis},
year = {2020},
journal = {Stem Cell Reports},
author = {Yang, Weiwei and Yang, Weiwei and Trahan, G. and Howell, Elizabeth D. and Speck, N. and Jones, Kenneth L. and Gillen, A. and Riemondy, K. and Hesselberth, J. and Bryder, D. and Bryder, D. and Ernst, P.}
}
Abstract
Summary The Mixed Lineage Leukemia (MLL1, KMT2A) gene is critical for development and maintenance of hematopoietic stem cells (HSCs), however, whether this protein is limiting for HSC development is unknown due to lack of physiologic model systems. Here, we develop an MLL1-inducible embryonic stem cell (ESC) system and show that induction of wild-type MLL1 during ESC differentiation selectively increases hematopoietic potential from a transitional c-Kit+/Cd41+ population in the embryoid body and also at sites of hematopoiesis in embryos. Single-cell sequencing analysis illustrates inherent heterogeneity of the c-Kit+/Cd41+ population and demonstrates that MLL1 induction shifts its composition toward multilineage hematopoietic identities. Surprisingly, this does not occur through increasing Hox or other canonical MLL1 targets but 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 in the endothelial to hematopoietic transition and demonstrate that MLL1 actives this axis.