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Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment

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@article{68c3b227388e4770aab16ced97789479,
title = "Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment",
abstract = "Hematopoietic stem cells (HSCs) are considered a heterogeneous cell population. To further resolve the HSC compartment, we characterized a retinoic acid (RA) reporter mouse line. Sub-fractionation of the HSC compartment in RA-CFP reporter mice demonstrated that RA-CFP-dim HSCs were largely non-proliferative and displayed superior engraftment potential in comparison with RA-CFP-bright HSCs. Gene expression analysis demonstrated higher expression of RA-target genes in RA-CFP-dim HSCs, in contrast to the RA-CFP reporter expression, but both RA-CFP-dim and RA-CFP-bright HSCs responded efficiently to RA in vitro. Single-cell RNA sequencing (RNA-seq) of >1,200 HSCs showed that differences in cell cycle activity constituted the main driver of transcriptional heterogeneity in HSCs. Moreover, further analysis of the single-cell RNA-seq data revealed that stochastic low-level expression of distinct lineage-affiliated transcriptional programs is a common feature of HSCs. Collectively, this work demonstrates the utility of the RA-CFP reporter line as a tool for the isolation of superior HSCs.",
author = "Lauridsen, {Felicia Kathrine Bratt} and Jensen, {Tanja Lyholm} and Nicolas Rapin and Derya Aslan and Wilhelmson, {Anna Sofia} and Sachin Pundhir and Matilda Rehn and Franziska Paul and Amir Giladi and Hasemann, {Marie Sigurd} and Palle Serup and Ido Amit and Porse, {Bo Torben}",
note = "Copyright {\circledC} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = "7",
day = "17",
doi = "10.1016/j.celrep.2018.06.057",
language = "English",
volume = "24",
pages = "766--780",
journal = "Cell Reports",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment

AU - Lauridsen, Felicia Kathrine Bratt

AU - Jensen, Tanja Lyholm

AU - Rapin, Nicolas

AU - Aslan, Derya

AU - Wilhelmson, Anna Sofia

AU - Pundhir, Sachin

AU - Rehn, Matilda

AU - Paul, Franziska

AU - Giladi, Amir

AU - Hasemann, Marie Sigurd

AU - Serup, Palle

AU - Amit, Ido

AU - Porse, Bo Torben

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018/7/17

Y1 - 2018/7/17

N2 - Hematopoietic stem cells (HSCs) are considered a heterogeneous cell population. To further resolve the HSC compartment, we characterized a retinoic acid (RA) reporter mouse line. Sub-fractionation of the HSC compartment in RA-CFP reporter mice demonstrated that RA-CFP-dim HSCs were largely non-proliferative and displayed superior engraftment potential in comparison with RA-CFP-bright HSCs. Gene expression analysis demonstrated higher expression of RA-target genes in RA-CFP-dim HSCs, in contrast to the RA-CFP reporter expression, but both RA-CFP-dim and RA-CFP-bright HSCs responded efficiently to RA in vitro. Single-cell RNA sequencing (RNA-seq) of >1,200 HSCs showed that differences in cell cycle activity constituted the main driver of transcriptional heterogeneity in HSCs. Moreover, further analysis of the single-cell RNA-seq data revealed that stochastic low-level expression of distinct lineage-affiliated transcriptional programs is a common feature of HSCs. Collectively, this work demonstrates the utility of the RA-CFP reporter line as a tool for the isolation of superior HSCs.

AB - Hematopoietic stem cells (HSCs) are considered a heterogeneous cell population. To further resolve the HSC compartment, we characterized a retinoic acid (RA) reporter mouse line. Sub-fractionation of the HSC compartment in RA-CFP reporter mice demonstrated that RA-CFP-dim HSCs were largely non-proliferative and displayed superior engraftment potential in comparison with RA-CFP-bright HSCs. Gene expression analysis demonstrated higher expression of RA-target genes in RA-CFP-dim HSCs, in contrast to the RA-CFP reporter expression, but both RA-CFP-dim and RA-CFP-bright HSCs responded efficiently to RA in vitro. Single-cell RNA sequencing (RNA-seq) of >1,200 HSCs showed that differences in cell cycle activity constituted the main driver of transcriptional heterogeneity in HSCs. Moreover, further analysis of the single-cell RNA-seq data revealed that stochastic low-level expression of distinct lineage-affiliated transcriptional programs is a common feature of HSCs. Collectively, this work demonstrates the utility of the RA-CFP reporter line as a tool for the isolation of superior HSCs.

U2 - 10.1016/j.celrep.2018.06.057

DO - 10.1016/j.celrep.2018.06.057

M3 - Journal article

VL - 24

SP - 766

EP - 780

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -

ID: 54960009