TitleChromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis.
Publication TypeJournal Article
Year of Publication2017
AuthorsPalpant NJ, Wang Y, Hadland B, Zaunbrecher RJ, Redd M, Jones D, Pabon L, Jain R, Epstein J, Ruzzo WL, Zheng Y, Bernstein I, Margolin A, Murry CE
JournalCell Rep
Date or Month Published2017 Aug 15

We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR(+)/CD34(+) endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells. Using HOPX reporter and knockout hESCs, we show that HOPX regulates blood formation. Loss of HOPX does not impact endothelial fate specification but markedly reduces primitive hematopoiesis, acting at least in part through failure to suppress Wnt/β-catenin signaling. Thus, chromatin state analysis permits identification of regulators of mesodermal specification, including a conserved role for HOPX in governing primitive hematopoiesis.

Alternate JournalCell Rep
Citation Key14131
PubMed ID28813672