Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing

Roy Drissen; Natalija Buza-Vidas; Petter Woll; Supat Thongjuea; Adriana Gambardella; Alice Giustacchini; Elena Mancini; Alya Zriwil; Michael Lutteropp; Amit Grover; Adam Mead; Ewa Sitnicka; Sten Eirik W Jacobsen; Claus Nerlov

doi:10.1038/ni.3412

Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing

Roy Drissen, Natalija Buza-Vidas, Petter Woll, Supat Thongjuea, Adriana Gambardella, Alice Giustacchini, Elena Mancini, Alya Zriwil, Michael Lutteropp, Amit Grover, Adam Mead, Ewa Sitnicka, Sten Eirik W Jacobsen, Claus Nerlov

Research output: Contribution to journal › Article › peer-review

Abstract

According to current models of hematopoiesis, lymphoid-primed multi-potent progenitors (LMPPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)Flt3(hi)) and common myeloid progenitors (CMPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)CD41(hi)) establish an early branch point for separate lineage-commitment pathways from hematopoietic stem cells, with the notable exception that both pathways are proposed to generate all myeloid innate immune cell types through the same myeloid-restricted pre-granulocyte-macrophage progenitor (pre-GM) (Lin(-)Sca-1(-)c-Kit(+)CD41(-)FcγRII/III(-)CD150(-)CD105(-)). By single-cell transcriptome profiling of pre-GMs, we identified distinct myeloid differentiation pathways: a pathway expressing the gene encoding the transcription factor GATA-1 generated mast cells, eosinophils, megakaryocytes and erythroid cells, and a pathway lacking expression of that gene generated monocytes, neutrophils and lymphocytes. These results identify an early hematopoietic-lineage bifurcation that separates the myeloid lineages before their segregation from other hematopoietic-lineage potential.

Original language	English
Pages (from-to)	666-676
Journal	Nature Immunology
Volume	17
Issue number	6
Early online date	2016 Apr 4
DOIs	https://doi.org/10.1038/ni.3412
Publication status	Published - 2016 Jun

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Immunology

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Drissen, R., Buza-Vidas, N., Woll, P., Thongjuea, S., Gambardella, A., Giustacchini, A., Mancini, E., Zriwil, A., Lutteropp, M., Grover, A., Mead, A., Sitnicka, E., Jacobsen, S. E. W., & Nerlov, C. (2016). Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing. Nature Immunology, 17(6), 666-676. https://doi.org/10.1038/ni.3412

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title = "Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing",

abstract = "According to current models of hematopoiesis, lymphoid-primed multi-potent progenitors (LMPPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)Flt3(hi)) and common myeloid progenitors (CMPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)CD41(hi)) establish an early branch point for separate lineage-commitment pathways from hematopoietic stem cells, with the notable exception that both pathways are proposed to generate all myeloid innate immune cell types through the same myeloid-restricted pre-granulocyte-macrophage progenitor (pre-GM) (Lin(-)Sca-1(-)c-Kit(+)CD41(-)FcγRII/III(-)CD150(-)CD105(-)). By single-cell transcriptome profiling of pre-GMs, we identified distinct myeloid differentiation pathways: a pathway expressing the gene encoding the transcription factor GATA-1 generated mast cells, eosinophils, megakaryocytes and erythroid cells, and a pathway lacking expression of that gene generated monocytes, neutrophils and lymphocytes. These results identify an early hematopoietic-lineage bifurcation that separates the myeloid lineages before their segregation from other hematopoietic-lineage potential.",

author = "Roy Drissen and Natalija Buza-Vidas and Petter Woll and Supat Thongjuea and Adriana Gambardella and Alice Giustacchini and Elena Mancini and Alya Zriwil and Michael Lutteropp and Amit Grover and Adam Mead and Ewa Sitnicka and Jacobsen, {Sten Eirik W} and Claus Nerlov",

year = "2016",

month = jun,

doi = "10.1038/ni.3412",

language = "English",

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pages = "666--676",

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T1 - Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing

AU - Drissen, Roy

AU - Buza-Vidas, Natalija

AU - Woll, Petter

AU - Thongjuea, Supat

AU - Gambardella, Adriana

AU - Giustacchini, Alice

AU - Mancini, Elena

AU - Zriwil, Alya

AU - Lutteropp, Michael

AU - Grover, Amit

AU - Mead, Adam

AU - Sitnicka, Ewa

AU - Jacobsen, Sten Eirik W

AU - Nerlov, Claus

PY - 2016/6

Y1 - 2016/6

N2 - According to current models of hematopoiesis, lymphoid-primed multi-potent progenitors (LMPPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)Flt3(hi)) and common myeloid progenitors (CMPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)CD41(hi)) establish an early branch point for separate lineage-commitment pathways from hematopoietic stem cells, with the notable exception that both pathways are proposed to generate all myeloid innate immune cell types through the same myeloid-restricted pre-granulocyte-macrophage progenitor (pre-GM) (Lin(-)Sca-1(-)c-Kit(+)CD41(-)FcγRII/III(-)CD150(-)CD105(-)). By single-cell transcriptome profiling of pre-GMs, we identified distinct myeloid differentiation pathways: a pathway expressing the gene encoding the transcription factor GATA-1 generated mast cells, eosinophils, megakaryocytes and erythroid cells, and a pathway lacking expression of that gene generated monocytes, neutrophils and lymphocytes. These results identify an early hematopoietic-lineage bifurcation that separates the myeloid lineages before their segregation from other hematopoietic-lineage potential.

AB - According to current models of hematopoiesis, lymphoid-primed multi-potent progenitors (LMPPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)Flt3(hi)) and common myeloid progenitors (CMPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)CD41(hi)) establish an early branch point for separate lineage-commitment pathways from hematopoietic stem cells, with the notable exception that both pathways are proposed to generate all myeloid innate immune cell types through the same myeloid-restricted pre-granulocyte-macrophage progenitor (pre-GM) (Lin(-)Sca-1(-)c-Kit(+)CD41(-)FcγRII/III(-)CD150(-)CD105(-)). By single-cell transcriptome profiling of pre-GMs, we identified distinct myeloid differentiation pathways: a pathway expressing the gene encoding the transcription factor GATA-1 generated mast cells, eosinophils, megakaryocytes and erythroid cells, and a pathway lacking expression of that gene generated monocytes, neutrophils and lymphocytes. These results identify an early hematopoietic-lineage bifurcation that separates the myeloid lineages before their segregation from other hematopoietic-lineage potential.

U2 - 10.1038/ni.3412

DO - 10.1038/ni.3412

M3 - Article

C2 - 27043410

SN - 1529-2908

VL - 17

SP - 666

EP - 676

JO - Nature Immunology

JF - Nature Immunology

IS - 6

ER -

Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing

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