POT1a deficiency in mesenchymal niches perturbs B-lymphopoiesis.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
29 09 2023
29 09 2023
Historique:
received:
19
04
2022
accepted:
18
09
2023
medline:
2
10
2023
pubmed:
29
9
2023
entrez:
29
9
2023
Statut:
epublish
Résumé
Protection of telomeres 1a (POT1a) is a telomere binding protein. A decrease of POT1a is related to myeloid-skewed haematopoiesis with ageing, suggesting that protection of telomeres is essential to sustain multi-potency. Since mesenchymal stem cells (MSCs) are a constituent of the hematopoietic niche in bone marrow, their dysfunction is associated with haematopoietic failure. However, the importance of telomere protection in MSCs has yet to be elucidated. Here, we show that genetic deletion of POT1a in MSCs leads to intracellular accumulation of fatty acids and excessive ROS and DNA damage, resulting in impaired osteogenic-differentiation. Furthermore, MSC-specific POT1a deficient mice exhibited skeletal retardation due to reduction of IL-7 producing bone lining osteoblasts. Single-cell gene expression profiling of bone marrow from POT1a deficient mice revealed that B-lymphopoiesis was selectively impaired. These results demonstrate that bone marrow microenvironments composed of POT1a deficient MSCs fail to support B-lymphopoiesis, which may underpin age-related myeloid-bias in haematopoiesis.
Identifiants
pubmed: 37773433
doi: 10.1038/s42003-023-05374-0
pii: 10.1038/s42003-023-05374-0
pmc: PMC10541440
doi:
Substances chimiques
Telomere-Binding Proteins
0
POT1 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
996Informations de copyright
© 2023. Springer Nature Limited.
Références
Blood. 2007 May 1;109(9):3706-12
pubmed: 17227831
Nat Immunol. 2019 Feb;20(2):163-172
pubmed: 30643263
Cell. 2006 Jul 14;126(1):63-77
pubmed: 16839877
Genes Dev. 2005 Sep 15;19(18):2100-10
pubmed: 16166375
Cell. 2004 Oct 29;119(3):355-68
pubmed: 15507207
Blood. 2011 Dec 1;118(23):6068-77
pubmed: 21948176
Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16976-81
pubmed: 18957542
J Biol Chem. 2018 Oct 12;293(41):16019-16027
pubmed: 30150300
Nat Med. 2018 Jun;24(6):782-791
pubmed: 29736022
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Cell. 2015 May 21;161(5):1202-1214
pubmed: 26000488
Biochim Biophys Acta. 2016 Oct;1861(10):1525-34
pubmed: 26996746
Br J Haematol. 2017 Nov;179(4):669-673
pubmed: 27480905
Circ Res. 2012 Apr 27;110(9):1226-37
pubmed: 22539756
Nature. 2010 Mar 25;464(7288):520-8
pubmed: 20336134
Nat Commun. 2017 Oct 6;8(1):804
pubmed: 28986560
Nature. 2011 Feb 17;470(7334):359-65
pubmed: 21307849
Nat Biotechnol. 2019 Apr;37(4):451-460
pubmed: 30899105
Immunity. 2016 Jun 21;44(6):1434-43
pubmed: 27317262
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nature. 2013 Mar 14;495(7440):231-5
pubmed: 23434755
Commun Biol. 2020 Dec 4;3(1):736
pubmed: 33277618
Nature. 2010 Aug 12;466(7308):829-34
pubmed: 20703299
iScience. 2020 Oct 07;23(11):101654
pubmed: 33103089
Haematologica. 2010 Jul;95(7):1081-9
pubmed: 20179085
J Clin Invest. 2014 Jan;124(1):353-66
pubmed: 24316971
Nature. 2013 Oct 31;502(7473):637-43
pubmed: 24107994
Nat Rev Mol Cell Biol. 2019 May;20(5):303-320
pubmed: 30745579
PLoS One. 2010 Jul 26;5(7):e11782
pubmed: 20668686
Blood. 2004 May 1;103(9):3258-64
pubmed: 14726388
Transfus Med Hemother. 2008 Jun;35(3):216-27
pubmed: 21547119
Cell. 2013 Oct 10;155(2):345-356
pubmed: 24120135
Int J Mol Sci. 2021 Apr 30;22(9):
pubmed: 33946412
Nat Med. 2012 Sep;18(9):1350-8
pubmed: 22902876
Cell. 1994 Dec 30;79(7):1147-56
pubmed: 8001151
J Exp Med. 2013 Jul 1;210(7):1351-67
pubmed: 23776077
Front Immunol. 2021 Mar 15;12:631279
pubmed: 33790904
Stem Cell Rev Rep. 2021 Dec;17(6):2178-2192
pubmed: 34410592
Mol Cell Biol. 2009 Jan;29(1):229-40
pubmed: 18936156
Cell Mol Biol Lett. 2022 Aug 19;27(1):69
pubmed: 35986247
Front Cell Dev Biol. 2021 Feb 09;9:637725
pubmed: 33634139
Cell Stem Cell. 2013 Jan 3;12(1):62-74
pubmed: 23290137
Nat Cell Biol. 2017 Mar;19(3):214-223
pubmed: 28218906
Blood. 2015 Jan 29;125(5):793-802
pubmed: 25499762
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Cell. 2006 Jul 14;126(1):49-62
pubmed: 16839876
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Immunity. 2010 Sep 24;33(3):387-99
pubmed: 20850355
Nat Rev Immunol. 2008 Sep;8(9):726-36
pubmed: 19172693
Nature. 2012 Jan 25;481(7382):457-62
pubmed: 22281595
Genes Dev. 2014 Jan 15;28(2):153-66
pubmed: 24449270
Immunity. 2006 Dec;25(6):977-88
pubmed: 17174120
Curr Stem Cell Res Ther. 2016;11(3):216-25
pubmed: 25986621