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Open AccessArticle

Conventional Co-Housing Modulates Murine Gut Microbiota and Hematopoietic Gene Expression

1
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
2
Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
3
Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
4
Center for Human Immunology and Autoimmunity, National Institutes of Health, Bethesda, MD 20892, USA
5
Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6143; https://doi.org/10.3390/ijms21176143
Received: 28 July 2020 / Revised: 21 August 2020 / Accepted: 21 August 2020 / Published: 26 August 2020
(This article belongs to the Special Issue Gut Microbiota-Host Interactions: From Symbiosis to Dysbiosis)
Specific-pathogen-free (SPF) mice have improved hematopoietic characteristics relative to germ-free mice, however, it is not clear whether improvements in hematopoietic traits will continue when the level of microorganism exposure is further increased. We co-housed SPF C57BL/6 mice in a conventional facility (CVT) and found a significant increase in gut microbiota diversity along with increased levels of myeloid cells and T cells, especially effector memory T cells. Through single cell RNA sequencing of sorted KL (c-Kit+Lin) cells, we imputed a decline in long-term hematopoietic stem cells and an increase in granulocyte-monocyte progenitors in CVT mice with up-regulation of genes associated with cell survival. Bone marrow transplantation through competitive repopulation revealed a significant increase in KSL (c-Kit+Sca-1+Lin) cell reconstitution in recipients of CVT donor cells which occurred when donors were co-housed for both one and twelve months. However, there was minimal to no gain in mature blood cell engraftment in recipients of CVT donor cells relative to those receiving SPF donor cells. We conclude that co-housing SPF mice with mice born in a conventional facility increased gut microbiota diversity, augmented myeloid cell production and T cell activation, stimulated KSL cell reconstitution, and altered hematopoietic gene expression. View Full-Text
Keywords: mice; specific pathogen free; conventional co-housing; gut microbiota; single cell RNA-seq; hematopoietic stem and progenitor cells mice; specific pathogen free; conventional co-housing; gut microbiota; single cell RNA-seq; hematopoietic stem and progenitor cells
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Chen, J.; Zhang, S.; Feng, X.; Wu, Z.; Dubois, W.; Thovarai, V.; Ahluwalia, S.; Gao, S.; Chen, J.; Peat, T.; Sen, S.K.; Trinchieri, G.; Young, N.S.; Mock, B.A. Conventional Co-Housing Modulates Murine Gut Microbiota and Hematopoietic Gene Expression. Int. J. Mol. Sci. 2020, 21, 6143.

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