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Macrophage colony-stimulating factor receptor marks and regulates a fetal myeloid-primed B-cell progenitor in mice

Zriwil, Alya LU ; Böiers, Charlotta LU ; Wittmann, Lilian LU ; Green, Joanna C A; Woll, Petter S.; Jacobsen, Sten Eirik W LU and Sitnicka, Ewa LU (2016) In Blood 128(2). p.217-226
Abstract

Although it is well established that unique B-cell lineages develop through distinct regulatory mechanisms during embryonic development, much less is understood about the differences between embryonic and adult B-cell progenitor cells, likely to underpin the genetics and biology of infant and childhood PreB acute lymphoblastic leukemia (PreB-ALL), initiated by distinct leukemia-initiating translocations during embryonic development. Herein, we establish that a distinct subset of the earliest CD19+ B-cell progenitors emerging in the E13.5 mouse fetal liver express the colony-stimulating factor-1 receptor (CSF1R), previously thought to be expressed, and play a lineage-restricted role in development of myeloid lineages, and... (More)

Although it is well established that unique B-cell lineages develop through distinct regulatory mechanisms during embryonic development, much less is understood about the differences between embryonic and adult B-cell progenitor cells, likely to underpin the genetics and biology of infant and childhood PreB acute lymphoblastic leukemia (PreB-ALL), initiated by distinct leukemia-initiating translocations during embryonic development. Herein, we establish that a distinct subset of the earliest CD19+ B-cell progenitors emerging in the E13.5 mouse fetal liver express the colony-stimulating factor-1 receptor (CSF1R), previously thought to be expressed, and play a lineage-restricted role in development of myeloid lineages, and macrophages in particular. These early embryonic CSF1R+CD19+ ProB cells also express multiple other myeloid genes and, in line with this, possess residual myeloid as well as B-cell, but not T-cell lineage potential. Notably, these CSF1R+ myeloid-primed ProB cells are uniquely present in a narrow window of embryonic fetal liver hematopoiesis and do not persist in adult bone marrow. Moreover, analysis of CSF1R-deficient mice establishes a distinct role of CSF1R in fetal B-lymphopoiesis. CSF1R+ myeloid-primed embryonic ProB cells are relevant for infant and childhood PreB-ALLs, which frequently have a bi-phenotypic B-myeloid phenotype, and in which CSF1R-rearrangements have recently been reported.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
128
issue
2
pages
10 pages
publisher
American Society of Hematology
external identifiers
  • scopus:84994016174
  • wos:000383830000013
ISSN
0006-4971
DOI
10.1182/blood-2016-01-693887
language
English
LU publication?
yes
id
367b2eed-4d17-4f84-b221-2aae431751f2
date added to LUP
2016-12-05 08:54:07
date last changed
2017-08-13 05:01:21
@article{367b2eed-4d17-4f84-b221-2aae431751f2,
  abstract     = {<p>Although it is well established that unique B-cell lineages develop through distinct regulatory mechanisms during embryonic development, much less is understood about the differences between embryonic and adult B-cell progenitor cells, likely to underpin the genetics and biology of infant and childhood PreB acute lymphoblastic leukemia (PreB-ALL), initiated by distinct leukemia-initiating translocations during embryonic development. Herein, we establish that a distinct subset of the earliest CD19<sup>+</sup> B-cell progenitors emerging in the E13.5 mouse fetal liver express the colony-stimulating factor-1 receptor (CSF1R), previously thought to be expressed, and play a lineage-restricted role in development of myeloid lineages, and macrophages in particular. These early embryonic CSF1R<sup>+</sup>CD19<sup>+</sup> ProB cells also express multiple other myeloid genes and, in line with this, possess residual myeloid as well as B-cell, but not T-cell lineage potential. Notably, these CSF1R<sup>+</sup> myeloid-primed ProB cells are uniquely present in a narrow window of embryonic fetal liver hematopoiesis and do not persist in adult bone marrow. Moreover, analysis of CSF1R-deficient mice establishes a distinct role of CSF1R in fetal B-lymphopoiesis. CSF1R<sup>+</sup> myeloid-primed embryonic ProB cells are relevant for infant and childhood PreB-ALLs, which frequently have a bi-phenotypic B-myeloid phenotype, and in which CSF1R-rearrangements have recently been reported.</p>},
  author       = {Zriwil, Alya and Böiers, Charlotta and Wittmann, Lilian and Green, Joanna C A and Woll, Petter S. and Jacobsen, Sten Eirik W and Sitnicka, Ewa},
  issn         = {0006-4971},
  language     = {eng},
  number       = {2},
  pages        = {217--226},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Macrophage colony-stimulating factor receptor marks and regulates a fetal myeloid-primed B-cell progenitor in mice},
  url          = {http://dx.doi.org/10.1182/blood-2016-01-693887},
  volume       = {128},
  year         = {2016},
}