The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification.
Yi-Chien Lu, Chad Sanada, Juliana Xavier-Ferrucio, Lin Wang, Ping-Xia Zhang, H Leighton Grimes, Meenakshi Venkatasubramanian, Kashish Chetal, Bruce Aronow, Nathan Salomonis, Diane S Krause
Author Information
- Yi-Chien Lu: 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.
- Chad Sanada: Department of Laboratory Medicine and Yale Stem Cell Center, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
- Juliana Xavier-Ferrucio: Department of Laboratory Medicine and Yale Stem Cell Center, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
- Lin Wang: Department of Laboratory Medicine and Yale Stem Cell Center, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
- Ping-Xia Zhang: Department of Laboratory Medicine and Yale Stem Cell Center, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
- H Leighton Grimes: 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.
- Meenakshi Venkatasubramanian: Division of Biomedical Informatics, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
- Kashish Chetal: Division of Biomedical Informatics, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
- Bruce Aronow: 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.
- Nathan Salomonis: 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.
- Diane S Krause: Department of Laboratory Medicine and Yale Stem Cell Center, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
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.
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Cell Cycle
Cell Lineage
Gene Expression Regulation
Gene Regulatory Networks
HEK293 Cells
High-Throughput Nucleotide Sequencing
Humans
Megakaryocyte-Erythroid Progenitor Cells
Proto-Oncogene Proteins c-myc
Reproducibility of Results
Signal Transduction
Transcription, Genetic
Tumor Suppressor Protein p53
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
MAX protein, human
MYC protein, human
Proto-Oncogene Proteins c-myc
Tumor Suppressor Protein p53
