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The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification
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 sequenc...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336197/ https://www.ncbi.nlm.nih.gov/pubmed/30463007 http://dx.doi.org/10.1016/j.celrep.2018.10.084 |
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author | Lu, Yi-Chien Sanada, Chad Xavier-Ferrucio, Juliana Wang, Lin Zhang, Ping-Xia Leighton Grimes, H. Venkatasubramanian, Meenakshi Chetal, Kashish Aronow, Bruce Salomonis, Nathan Krause, Diane S. |
author_facet | Lu, Yi-Chien Sanada, Chad Xavier-Ferrucio, Juliana Wang, Lin Zhang, Ping-Xia Leighton Grimes, H. Venkatasubramanian, Meenakshi Chetal, Kashish Aronow, Bruce Salomonis, Nathan Krause, Diane S. |
author_sort | Lu, Yi-Chien |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6336197 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-63361972019-01-17 The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification Lu, Yi-Chien Sanada, Chad Xavier-Ferrucio, Juliana Wang, Lin Zhang, Ping-Xia Leighton Grimes, H. Venkatasubramanian, Meenakshi Chetal, Kashish Aronow, Bruce Salomonis, Nathan Krause, Diane S. Cell Rep Article 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. 2018-11-20 /pmc/articles/PMC6336197/ /pubmed/30463007 http://dx.doi.org/10.1016/j.celrep.2018.10.084 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Lu, Yi-Chien Sanada, Chad Xavier-Ferrucio, Juliana Wang, Lin Zhang, Ping-Xia Leighton Grimes, H. Venkatasubramanian, Meenakshi Chetal, Kashish Aronow, Bruce Salomonis, Nathan Krause, Diane S. The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification |
title | The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification |
title_full | The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification |
title_fullStr | The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification |
title_full_unstemmed | The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification |
title_short | The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification |
title_sort | molecular signature of megakaryocyte-erythroid progenitors reveals a role for the cell cycle in fate specification |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336197/ https://www.ncbi.nlm.nih.gov/pubmed/30463007 http://dx.doi.org/10.1016/j.celrep.2018.10.084 |
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