Format

Send to

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

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

Author information

1
Department of Laboratory Medicine and Yale Stem Cell Center, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. Electronic address: yi-chien.lu@yale.edu.
2
Department of Laboratory Medicine and Yale Stem Cell Center, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
3
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH 45229, USA.
4
Division of Biomedical Informatics, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
5
Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH 45229, USA; Division of Biomedical Informatics, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.

Abstract

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.

PMID:
30463007
DOI:
10.1016/j.celrep.2018.10.084
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center