Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis

Nathan J. Palpant, Yuliang Wang, Brandon Hadland, Rebecca J. Zaunbrecher, Meredith Redd, Daniel Jones, Lil Pabon, Rajan Jain, Jonathan Epstein, Walter L. Ruzzo, Ying Zheng, Irwin Bernstein, Adam Margolin, Charles E. Murry

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1597-1608
Number of pages12
JournalCell Reports
Volume20
Issue number7
DOIs
StatePublished - Aug 15 2017

Keywords

  • Wnt signaling
  • cardiac
  • cardiovascular
  • chromatin dynamics
  • differentiation
  • epigenetics
  • genome engineering
  • hematopoiesis
  • human pluripotent stem cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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