PMID- 31332039
OWN - NLM
STAT- MEDLINE
DCOM- 20200706
LR  - 20200725
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 146
IP  - 14
DP  - 2019 Jul 22
TI  - The lymphoid-associated interleukin 7 receptor (IL7R) regulates tissue-resident 
      macrophage development.
LID - 10.1242/dev.176180 [doi]
LID - dev176180
AB  - The discovery of a fetal origin for tissue-resident macrophages (trMacs) has 
      inspired an intense search for the mechanisms underlying their development. Here, 
      we performed in vivo lineage tracing of cells with an expression history of 
      IL7Ralpha, a marker exclusively associated with the lymphoid lineage in adult 
      hematopoiesis. Surprisingly, we found that Il7r-Cre labeled fetal-derived, adult 
      trMacs. Labeling was almost complete in some tissues and partial in others. The 
      putative progenitors of trMacs, yolk sac (YS) erythromyeloid progenitors, did not 
      express IL7R, and YS hematopoiesis was unperturbed in IL7R-deficient mice. In 
      contrast, tracking of IL7Ralpha message levels, surface expression, and 
      Il7r-Cre-mediated labeling across fetal development revealed dynamic regulation 
      of Il7r mRNA expression and rapid upregulation of IL7Ralpha surface protein upon 
      transition from monocyte to macrophage within fetal tissues. Fetal monocyte 
      differentiation in vitro produced IL7R(+) macrophages, supporting a direct 
      progenitor-progeny relationship. Additionally, blockade of IL7R function during 
      late gestation specifically impaired the establishment of fetal-derived trMacs in 
      vivo These data provide evidence for a distinct function of IL7Ralpha in fetal 
      myelopoiesis and identify IL7R as a novel regulator of trMac development.
CI  - (c) 2019. Published by The Company of Biologists Ltd.
FAU - Leung, Gabriel A
AU  - Leung GA
AD  - Quantitative and Systems Biology Program, University of California-Merced, 
      Merced, CA 95343, USA.
FAU - Cool, Taylor
AU  - Cool T
AD  - Institute for the Biology of Stem Cells, University of California-Santa Cruz, 
      Santa Cruz, CA 95064, USA.
AD  - Department of Biological Sciences, San Jose State University, San Jose, CA 95192, 
      USA.
AD  - Department of Molecular, Cell, and Developmental Biology, University of 
      California-Santa Cruz, Santa Cruz, CA 95064, USA.
FAU - Valencia, Clint H
AU  - Valencia CH
AD  - Molecular and Cell Biology Department, School of Natural Sciences, University of 
      California-Merced, Merced, CA 95343, USA.
FAU - Worthington, Atesh
AU  - Worthington A
AD  - Institute for the Biology of Stem Cells, University of California-Santa Cruz, 
      Santa Cruz, CA 95064, USA.
AD  - Department of Molecular, Cell, and Developmental Biology, University of 
      California-Santa Cruz, Santa Cruz, CA 95064, USA.
FAU - Beaudin, Anna E
AU  - Beaudin AE
AUID- ORCID: 0000-0002-8580-8660
AD  - Molecular and Cell Biology Department, School of Natural Sciences, University of 
      California-Merced, Merced, CA 95343, USA abeaudin@ucmerced.edu cforsber@ucsc.edu.
FAU - Forsberg, E Camilla
AU  - Forsberg EC
AUID- ORCID: 0000-0003-0715-9703
AD  - Institute for the Biology of Stem Cells, University of California-Santa Cruz, 
      Santa Cruz, CA 95064, USA abeaudin@ucmerced.edu cforsber@ucsc.edu.
AD  - Department of Biomolecular Engineering, University of California-Santa Cruz, 
      Santa Cruz, CA 95064, USA.
LA  - eng
GR  - R01 HL147081/HL/NHLBI NIH HHS/United States
GR  - K01 HL130753/HL/NHLBI NIH HHS/United States
GR  - T32 GM008646/GM/NIGMS NIH HHS/United States
GR  - R01 DK100917/DK/NIDDK NIH HHS/United States
GR  - F31 HL140781/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190722
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (interleukin-7 receptor, alpha chain)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/*genetics
MH  - Cell Lineage/*genetics
MH  - Embryo, Mammalian
MH  - Female
MH  - Fetus/metabolism
MH  - Hematopoiesis/genetics
MH  - Macrophages/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myelopoiesis/*genetics
MH  - Pregnancy
MH  - Receptors, Interleukin-7/*physiology
PMC - PMC6679362
OTO - NOTNLM
OT  - Developmental hematopoiesis
OT  - Hematopoietic stem cells
OT  - IL7R
OT  - Lineage tracing
OT  - Monocyte to macrophage differentiation
OT  - Mouse
OT  - Tissue-resident macrophages
COIS- Competing interestsThe authors declare no competing or financial interests.
EDAT- 2019/07/25 06:00
MHDA- 2020/07/07 06:00
PMCR- 2020/07/15
CRDT- 2019/07/24 06:00
PHST- 2019/01/30 00:00 [received]
PHST- 2019/06/25 00:00 [accepted]
PHST- 2019/07/24 06:00 [entrez]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2020/07/07 06:00 [medline]
PHST- 2020/07/15 00:00 [pmc-release]
AID - 146/14/dev176180 [pii]
AID - DEV176180 [pii]
AID - 10.1242/dev.176180 [doi]
PST - epublish
SO  - Development. 2019 Jul 22;146(14):dev176180. doi: 10.1242/dev.176180.