Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment
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Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment. / Lauridsen, Felicia KB.; Jensen, Tanja L.; Rapin, Nicolas; Aslan, Derya; Wilhelmson, Anna S.; Pundhir, Sachin; Rehn, Matilda; Paul, Franziska; Giladi, Amir; Hasemann, Marie Sigurd; Serup, Palle; Amit, Ido; Porse, Bo Torben.
In: Cell Reports, Vol. 24, No. 3, 2018, p. 766-780.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment
AU - Lauridsen, Felicia KB.
AU - Jensen, Tanja L.
AU - Rapin, Nicolas
AU - Aslan, Derya
AU - Wilhelmson, Anna S.
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
Y1 - 2018
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
C2 - 30021172
VL - 24
SP - 766
EP - 780
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 3
ER -
ID: 200815524