Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets

NIH Intramural Sequencing Center

doi:10.1016/j.molcel.2020.04.008

Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets

NIH Intramural Sequencing Center

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

86 Scopus citations

Abstract

Myelofibrosis (MF) is characterized by increased numbers of morphologically abnormal megakaryocytes (Mks). Single-cell RNA sequencing of >120,000 hematopoietic stem and progenitor cells demonstrated Mk-biased hematopoiesis across clinical and molecular MF subgroups. Mk progenitors were heterogeneous, with distinct expression of inflammatory mediators. Aberrant surface G6B expression on MF stem and progenitors could allow selective immunotherapeutic targeting of the MF clone.

Original language	English (US)
Pages (from-to)	477-492.e8
Journal	Molecular cell
Volume	78
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2020.04.008
State	Published - May 7 2020
Externally published	Yes

Keywords

G6B
TARGET-seq
bone marrow
fibrosis
immunotherapy
megakaryopoiesis
myeloproliferative neoplasm
platelets
single-cell multi-omics

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2020.04.008

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@article{ae6f4e887ed94fb2bd1154975be3e43d,

title = "Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets",

abstract = "Myelofibrosis (MF) is characterized by increased numbers of morphologically abnormal megakaryocytes (Mks). Single-cell RNA sequencing of >120,000 hematopoietic stem and progenitor cells demonstrated Mk-biased hematopoiesis across clinical and molecular MF subgroups. Mk progenitors were heterogeneous, with distinct expression of inflammatory mediators. Aberrant surface G6B expression on MF stem and progenitors could allow selective immunotherapeutic targeting of the MF clone.",

keywords = "G6B, TARGET-seq, bone marrow, fibrosis, immunotherapy, megakaryopoiesis, myeloproliferative neoplasm, platelets, single-cell multi-omics",

author = "{NIH Intramural Sequencing Center} and Bethan Psaila and Guanlin Wang and Alba Rodriguez-Meira and Rong Li and Heuston, {Elisabeth F.} and Lauren Murphy and Daniel Yee and Hitchcock, {Ian S.} and Nikolaos Sousos and Jennifer O'Sullivan and Stacie Anderson and Senis, {Yotis A.} and Weinberg, {Olga K.} and Calicchio, {Monica L.} and Deena Iskander and Daniel Royston and Dragana Milojkovic and Irene Roberts and Bodine, {David M.} and Supat Thongjuea and Mead, {Adam J.}",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

month = may,

day = "7",

doi = "10.1016/j.molcel.2020.04.008",

language = "English (US)",

volume = "78",

pages = "477--492.e8",

journal = "Molecular cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "3",

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TY - JOUR

T1 - Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets

AU - NIH Intramural Sequencing Center

AU - Psaila, Bethan

AU - Wang, Guanlin

AU - Rodriguez-Meira, Alba

AU - Li, Rong

AU - Heuston, Elisabeth F.

AU - Murphy, Lauren

AU - Yee, Daniel

AU - Hitchcock, Ian S.

AU - Sousos, Nikolaos

AU - O'Sullivan, Jennifer

AU - Anderson, Stacie

AU - Senis, Yotis A.

AU - Weinberg, Olga K.

AU - Calicchio, Monica L.

AU - Iskander, Deena

AU - Royston, Daniel

AU - Milojkovic, Dragana

AU - Roberts, Irene

AU - Bodine, David M.

AU - Thongjuea, Supat

AU - Mead, Adam J.

PY - 2020/5/7

Y1 - 2020/5/7

N2 - Myelofibrosis (MF) is characterized by increased numbers of morphologically abnormal megakaryocytes (Mks). Single-cell RNA sequencing of >120,000 hematopoietic stem and progenitor cells demonstrated Mk-biased hematopoiesis across clinical and molecular MF subgroups. Mk progenitors were heterogeneous, with distinct expression of inflammatory mediators. Aberrant surface G6B expression on MF stem and progenitors could allow selective immunotherapeutic targeting of the MF clone.

AB - Myelofibrosis (MF) is characterized by increased numbers of morphologically abnormal megakaryocytes (Mks). Single-cell RNA sequencing of >120,000 hematopoietic stem and progenitor cells demonstrated Mk-biased hematopoiesis across clinical and molecular MF subgroups. Mk progenitors were heterogeneous, with distinct expression of inflammatory mediators. Aberrant surface G6B expression on MF stem and progenitors could allow selective immunotherapeutic targeting of the MF clone.

KW - G6B

KW - TARGET-seq

KW - bone marrow

KW - fibrosis

KW - immunotherapy

KW - megakaryopoiesis

KW - myeloproliferative neoplasm

KW - platelets

KW - single-cell multi-omics

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UR - http://www.scopus.com/inward/citedby.url?scp=85084221538&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2020.04.008

DO - 10.1016/j.molcel.2020.04.008

M3 - Article

C2 - 32386542

AN - SCOPUS:85084221538

SN - 1097-2765

VL - 78

SP - 477-492.e8

JO - Molecular cell

JF - Molecular cell

IS - 3

ER -

Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets

Abstract

Keywords

ASJC Scopus subject areas

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