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From the same journal

Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal.

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Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal. / Shepherd, MS; Li, J; Wilson, NK; Oedekoven, CA; Li, J; Belmonte, M; Fink, J; Prick, JCM; Pask, DC; Hamilton, TL; Loeffler, D; Rao, A; Schröder, T; Göttgens, B; Green, AR; Kent, DG.

In: Blood, Vol. 132, No. 8, 23.08.2018, p. 791-803.

Research output: Contribution to journalArticlepeer-review

Harvard

Shepherd, MS, Li, J, Wilson, NK, Oedekoven, CA, Li, J, Belmonte, M, Fink, J, Prick, JCM, Pask, DC, Hamilton, TL, Loeffler, D, Rao, A, Schröder, T, Göttgens, B, Green, AR & Kent, DG 2018, 'Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal.', Blood, vol. 132, no. 8, pp. 791-803. https://doi.org/10.1182/blood-2017-12-821066

APA

Shepherd, MS., Li, J., Wilson, NK., Oedekoven, CA., Li, J., Belmonte, M., Fink, J., Prick, JCM., Pask, DC., Hamilton, TL., Loeffler, D., Rao, A., Schröder, T., Göttgens, B., Green, AR., & Kent, DG. (2018). Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal. Blood, 132(8), 791-803. https://doi.org/10.1182/blood-2017-12-821066

Vancouver

Shepherd MS, Li J, Wilson NK, Oedekoven CA, Li J, Belmonte M et al. Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal. Blood. 2018 Aug 23;132(8):791-803. https://doi.org/10.1182/blood-2017-12-821066

Author

Shepherd, MS ; Li, J ; Wilson, NK ; Oedekoven, CA ; Li, J ; Belmonte, M ; Fink, J ; Prick, JCM ; Pask, DC ; Hamilton, TL ; Loeffler, D ; Rao, A ; Schröder, T ; Göttgens, B ; Green, AR ; Kent, DG. / Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal. In: Blood. 2018 ; Vol. 132, No. 8. pp. 791-803.

Bibtex - Download

@article{093e86f74e4847a780acc8ac43d74183,
title = "Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal.",
abstract = "Recent advances in single-cell technologies have permitted the investigation of heterogeneous cell populations at previously unattainable resolution. Here we apply such approaches to resolve the molecular mechanisms driving disease in mouse hematopoietic stem cells (HSCs), using JAK2V617F mutant myeloproliferative neoplasms (MPNs) as a model. Single-cell gene expression and functional assays identified a subset of JAK2V617F mutant HSCs that display defective self-renewal. This defect is rescued at the single HSC level by crossing JAK2V617F mice with mice lacking TET2, the most commonly comutated gene in patients with MPN. Single-cell gene expression profiling of JAK2V617F-mutant HSCs revealed a loss of specific regulator genes, some of which were restored to normal levels in single TET2/JAK2 mutant HSCs. Of these, Bmi1 and, to a lesser extent, Pbx1 and Meis1 overexpression in JAK2-mutant HSCs could drive a disease phenotype and retain durable stem cell self-renewal in functional assays. Together, these single-cell approaches refine the molecules involved in clonal expansion of MPNs and have broad implications for deconstructing the molecular network of normal and malignant stem cells.",
author = "MS Shepherd and J Li and NK Wilson and CA Oedekoven and J Li and M Belmonte and J Fink and JCM Prick and DC Pask and TL Hamilton and D Loeffler and A Rao and T Schr{\"o}der and B G{\"o}ttgens and AR Green and DG Kent",
year = "2018",
month = aug,
day = "23",
doi = "10.1182/blood-2017-12-821066",
language = "English",
volume = "132",
pages = "791--803",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "8",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal.

AU - Shepherd, MS

AU - Li, J

AU - Wilson, NK

AU - Oedekoven, CA

AU - Li, J

AU - Belmonte, M

AU - Fink, J

AU - Prick, JCM

AU - Pask, DC

AU - Hamilton, TL

AU - Loeffler, D

AU - Rao, A

AU - Schröder, T

AU - Göttgens, B

AU - Green, AR

AU - Kent, DG

PY - 2018/8/23

Y1 - 2018/8/23

N2 - Recent advances in single-cell technologies have permitted the investigation of heterogeneous cell populations at previously unattainable resolution. Here we apply such approaches to resolve the molecular mechanisms driving disease in mouse hematopoietic stem cells (HSCs), using JAK2V617F mutant myeloproliferative neoplasms (MPNs) as a model. Single-cell gene expression and functional assays identified a subset of JAK2V617F mutant HSCs that display defective self-renewal. This defect is rescued at the single HSC level by crossing JAK2V617F mice with mice lacking TET2, the most commonly comutated gene in patients with MPN. Single-cell gene expression profiling of JAK2V617F-mutant HSCs revealed a loss of specific regulator genes, some of which were restored to normal levels in single TET2/JAK2 mutant HSCs. Of these, Bmi1 and, to a lesser extent, Pbx1 and Meis1 overexpression in JAK2-mutant HSCs could drive a disease phenotype and retain durable stem cell self-renewal in functional assays. Together, these single-cell approaches refine the molecules involved in clonal expansion of MPNs and have broad implications for deconstructing the molecular network of normal and malignant stem cells.

AB - Recent advances in single-cell technologies have permitted the investigation of heterogeneous cell populations at previously unattainable resolution. Here we apply such approaches to resolve the molecular mechanisms driving disease in mouse hematopoietic stem cells (HSCs), using JAK2V617F mutant myeloproliferative neoplasms (MPNs) as a model. Single-cell gene expression and functional assays identified a subset of JAK2V617F mutant HSCs that display defective self-renewal. This defect is rescued at the single HSC level by crossing JAK2V617F mice with mice lacking TET2, the most commonly comutated gene in patients with MPN. Single-cell gene expression profiling of JAK2V617F-mutant HSCs revealed a loss of specific regulator genes, some of which were restored to normal levels in single TET2/JAK2 mutant HSCs. Of these, Bmi1 and, to a lesser extent, Pbx1 and Meis1 overexpression in JAK2-mutant HSCs could drive a disease phenotype and retain durable stem cell self-renewal in functional assays. Together, these single-cell approaches refine the molecules involved in clonal expansion of MPNs and have broad implications for deconstructing the molecular network of normal and malignant stem cells.

U2 - 10.1182/blood-2017-12-821066

DO - 10.1182/blood-2017-12-821066

M3 - Article

VL - 132

SP - 791

EP - 803

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -