PMID- 36997537
OWN - NLM
STAT- MEDLINE
DCOM- 20230403
LR  - 20240214
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Mar 30
TI  - Primitive haematopoiesis in the human placenta gives rise to macrophages with 
      epigenetically silenced HLA-DR.
PG  - 1764
LID - 10.1038/s41467-023-37383-2 [doi]
LID - 1764
AB  - The earliest macrophages are generated during embryonic development from 
      erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. Although this 
      process is thought to be spatially restricted to the yolk sac in the mouse, in 
      humans, it remains poorly understood. Human foetal placental macrophages, or 
      Hofbauer cells (HBC), arise during the primitive haematopoietic wave ~18 days 
      post conception and lack expression of human leukocyte antigen (HLA) class II. 
      Here, we identify a population of placental erythro-myeloid progenitors (PEMPs) 
      in the early human placenta that have conserved features of primitive yolk sac 
      EMPs, including the lack of HLF expression. Using in vitro culture experiments we 
      demonstrate that PEMP generate HBC-like cells lacking HLA-DR expression. We find 
      the absence of HLA-DR in primitive macrophages is mediated via epigenetic 
      silencing of class II transactivator, CIITA, the master regulator of HLA class II 
      gene expression. These findings establish the human placenta as an additional 
      site of primitive haematopoiesis.
CI  - (c) 2023. Crown.
FAU - Thomas, Jake R
AU  - Thomas JR
AUID- ORCID: 0000-0003-0526-4470
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
AD  - Department of Pathology, University of Cambridge, Cambridge, UK.
AD  - Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
FAU - Appios, Anna
AU  - Appios A
AUID- ORCID: 0000-0002-7111-5126
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
AD  - Department of Pathology, University of Cambridge, Cambridge, UK.
FAU - Calderbank, Emily F
AU  - Calderbank EF
AUID- ORCID: 0000-0002-9559-6593
AD  - Department of Haematology and Wellcome and MRC Cambridge Stem Cell Institute, 
      University of Cambridge, Cambridge, UK.
FAU - Yoshida, Nagisa
AU  - Yoshida N
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
AD  - Department of Pathology, University of Cambridge, Cambridge, UK.
FAU - Zhao, Xiaohui
AU  - Zhao X
AUID- ORCID: 0000-0001-9922-2815
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
FAU - Hamilton, Russell S
AU  - Hamilton RS
AUID- ORCID: 0000-0002-0598-3793
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
FAU - Moffett, Ashley
AU  - Moffett A
AUID- ORCID: 0000-0002-8388-9073
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
AD  - Department of Pathology, University of Cambridge, Cambridge, UK.
FAU - Sharkey, Andrew
AU  - Sharkey A
AUID- ORCID: 0000-0002-5072-7748
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
AD  - Department of Pathology, University of Cambridge, Cambridge, UK.
FAU - Laurenti, Elisa
AU  - Laurenti E
AUID- ORCID: 0000-0002-9917-9092
AD  - Department of Haematology and Wellcome and MRC Cambridge Stem Cell Institute, 
      University of Cambridge, Cambridge, UK.
FAU - Hanna, Courtney W
AU  - Hanna CW
AUID- ORCID: 0000-0002-4063-5575
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. 
      cwh36@cam.ac.uk.
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge, UK. cwh36@cam.ac.uk.
FAU - McGovern, Naomi
AU  - McGovern N
AUID- ORCID: 0000-0001-5200-2698
AD  - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. 
      nm390@cam.ac.uk.
AD  - Department of Pathology, University of Cambridge, Cambridge, UK. nm390@cam.ac.uk.
LA  - eng
GR  - 204464/Z/16/Z/WT_/Wellcome Trust/United Kingdom
GR  - MC_PC_17230/MRC_/Medical Research Council/United Kingdom
GR  - BB/P002293/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - MR/P001092/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230330
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (HLA-DR Antigens)
SB  - IM
MH  - Humans
MH  - Female
MH  - Pregnancy
MH  - Animals
MH  - Mice
MH  - *Placenta
MH  - *Macrophages
MH  - HLA-DR Antigens/genetics
MH  - Hematopoiesis/genetics
MH  - Embryonic Development
PMC - PMC10063560
COIS- The authors declare no competing interests.
EDAT- 2023/03/31 06:00
MHDA- 2023/04/03 06:42
PMCR- 2023/03/30
CRDT- 2023/03/30 23:15
PHST- 2022/07/31 00:00 [received]
PHST- 2023/03/13 00:00 [accepted]
PHST- 2023/04/03 06:42 [medline]
PHST- 2023/03/30 23:15 [entrez]
PHST- 2023/03/31 06:00 [pubmed]
PHST- 2023/03/30 00:00 [pmc-release]
AID - 10.1038/s41467-023-37383-2 [pii]
AID - 37383 [pii]
AID - 10.1038/s41467-023-37383-2 [doi]
PST - epublish
SO  - Nat Commun. 2023 Mar 30;14(1):1764. doi: 10.1038/s41467-023-37383-2.