PMID- 31980634
OWN - NLM
STAT- MEDLINE
DCOM- 20200408
LR  - 20210123
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Jan 24
TI  - Erythroid differentiation regulator-1 induced by microbiota in early life drives 
      intestinal stem cell proliferation and regeneration.
PG  - 513
LID - 10.1038/s41467-019-14258-z [doi]
LID - 513
AB  - Gut microbiota and their metabolites are instrumental in regulating intestinal 
      homeostasis. However, early-life microbiota associated influences on intestinal 
      development remain incompletely understood. Here we demonstrate that co-housing 
      of germ-free (GF) mice with specific-pathogen free (SPF) mice at weaning (exGF) 
      results in altered intestinal gene expression. Our results reveal that one highly 
      differentially expressed gene, erythroid differentiation regulator-1 (Erdr1), is 
      induced during development in SPF but not GF or exGF mice and localizes to 
      Lgr5(+) stem cells and transit amplifying (TA) cells. Erdr1 functions to induce 
      Wnt signaling in epithelial cells, increase Lgr5(+) stem cell expansion, and 
      promote intestinal organoid growth. Additionally, Erdr1 accelerates scratch-wound 
      closure in vitro, increases Lgr5(+) intestinal stem cell regeneration following 
      radiation-induced injury in vivo, and enhances recovery from dextran sodium 
      sulfate (DSS)-induced colonic damage. Collectively, our findings indicate that 
      early-life microbiota controls Erdr1-mediated intestinal epithelial proliferation 
      and regeneration in response to mucosal damage.
FAU - Abo, Hirohito
AU  - Abo H
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, 100 Piedmont Ave, Atlanta, GA, 30303, USA.
FAU - Chassaing, Benoit
AU  - Chassaing B
AUID- ORCID: 0000-0002-4285-769X
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, 100 Piedmont Ave, Atlanta, GA, 30303, USA.
AD  - Neuroscience Institute and Institute for Biomedical Sciences, Georgia State 
      University, Atlanta, Georgia, USA.
AD  - INSERM, U1016, Paris, France.
AD  - Universite de Paris, Paris, France.
FAU - Harusato, Akihito
AU  - Harusato A
AUID- ORCID: 0000-0001-9204-1819
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, 100 Piedmont Ave, Atlanta, GA, 30303, USA.
FAU - Quiros, Miguel
AU  - Quiros M
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
FAU - Brazil, Jennifer C
AU  - Brazil JC
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
FAU - Ngo, Vu L
AU  - Ngo VL
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, 100 Piedmont Ave, Atlanta, GA, 30303, USA.
FAU - Viennois, Emilie
AU  - Viennois E
AD  - Center for Diagnostics and Therapeutics, Institute for Biomedical Sciences, 
      Georgia State University, Atlanta, GA, 30303, USA.
FAU - Merlin, Didier
AU  - Merlin D
AD  - Center for Diagnostics and Therapeutics, Institute for Biomedical Sciences, 
      Georgia State University, Atlanta, GA, 30303, USA.
AD  - Atlanta Veterans Affairs Medical Center, Decatur, GA, 30033, USA.
FAU - Gewirtz, Andrew T
AU  - Gewirtz AT
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, 100 Piedmont Ave, Atlanta, GA, 30303, USA.
FAU - Nusrat, Asma
AU  - Nusrat A
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
FAU - Denning, Timothy L
AU  - Denning TL
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, 100 Piedmont Ave, Atlanta, GA, 30303, USA. 
      tdenning@gsu.edu.
LA  - eng
GR  - R01 DK055679/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20200124
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Lgr5 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (erythroid differentiation regulator 1, mouse)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/genetics
MH  - Colitis/chemically induced/microbiology/pathology
MH  - Dextran Sulfate
MH  - Epithelial Cells/metabolism
MH  - Gene Expression Regulation
MH  - Germ-Free Life
MH  - Humans
MH  - Luciferases/metabolism
MH  - Membrane Proteins/*metabolism
MH  - Mice, Inbred C57BL
MH  - *Microbiota/genetics
MH  - Organoids/metabolism
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - *Regeneration
MH  - Stem Cells/*cytology/metabolism
MH  - Tumor Suppressor Proteins/*metabolism
MH  - Wnt Signaling Pathway/genetics
MH  - Wound Healing/genetics
PMC - PMC6981263
COIS- The authors declare no competing interests.
EDAT- 2020/01/26 06:00
MHDA- 2020/04/09 06:00
PMCR- 2020/01/24
CRDT- 2020/01/26 06:00
PHST- 2019/03/21 00:00 [received]
PHST- 2019/12/22 00:00 [accepted]
PHST- 2020/01/26 06:00 [entrez]
PHST- 2020/01/26 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2020/01/24 00:00 [pmc-release]
AID - 10.1038/s41467-019-14258-z [pii]
AID - 14258 [pii]
AID - 10.1038/s41467-019-14258-z [doi]
PST - epublish
SO  - Nat Commun. 2020 Jan 24;11(1):513. doi: 10.1038/s41467-019-14258-z.