The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification

Cell Rep. 2018 Nov 20;25(8):2083-2093.e4. doi: 10.1016/j.celrep.2018.10.084.


Megakaryocytic-erythroid progenitors (MEPs) give rise to the cells that produce red blood cells and platelets. Although the mechanisms underlying megakaryocytic (MK) and erythroid (E) maturation have been described, those controlling their specification from MEPs are unknown. Single-cell RNA sequencing of primary human MEPs, common myeloid progenitors (CMPs), megakaryocyte progenitors, and E progenitors revealed a distinct transitional MEP signature. Inferred regulatory transcription factors (TFs) were associated with differential expression of cell cycle regulators. Genetic manipulation of selected TFs validated their role in lineage specification and demonstrated coincident modulation of the cell cycle. Genetic and pharmacologic modulation demonstrated that cell cycle activation is sufficient to promote E versus MK specification. These findings, obtained from healthy human cells, lay a foundation to study the mechanisms underlying benign and malignant disease states of the megakaryocytic and E lineages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Cell Cycle*
  • Cell Lineage*
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • HEK293 Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Megakaryocyte-Erythroid Progenitor Cells / cytology*
  • Megakaryocyte-Erythroid Progenitor Cells / metabolism*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Reproducibility of Results
  • Signal Transduction
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / metabolism


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MAX protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53