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Conventional Co-Housing Modulates Murine Gut Microbiota and Hematopoietic Gene Expression
Jichun Chen1, Shuling Zhang2, Xingmin Feng1
1Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
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.
Insights
Increasing microbial exposure in specific-pathogen-free (SPF) mice enhances gut microbiota diversity and myeloid cell production. This shift stimulates hematopoietic stem cell reconstitution but does not improve mature blood cell engraftment.
Area of Science:
- Immunology
- Hematology
- Microbiome Research
Background:
- Specific-pathogen-free (SPF) mice exhibit superior hematopoietic characteristics compared to germ-free counterparts.
- The impact of further increasing microbial exposure on these hematopoietic traits remains unclear.
Purpose of the Study:
- To investigate the effects of increased microbial exposure on hematopoietic stem cells and immune cell populations in SPF mice.
- To determine if enhanced microbial exposure influences hematopoietic stem cell function and blood cell engraftment.
Main Methods:
- SPF C57BL/6 mice were co-housed with conventionally raised mice (CVT).
- Gut microbiota diversity, myeloid and T cell populations were analyzed.
- Single-cell RNA sequencing of c-Kit+Lin- (KL) cells was performed.
- Competitive bone marrow transplantation assays were conducted.
Main Results:
- Co-housing led to increased gut microbiota diversity, elevated myeloid and T cell levels (especially effector memory T cells).
- Single-cell RNA sequencing indicated a decrease in long-term hematopoietic stem cells and an increase in granulocyte-monocyte progenitors.
- Bone marrow transplantation showed enhanced c-Kit+Sca-1+Lin- (KSL) cell reconstitution from CVT donors.
- Mature blood cell engraftment showed minimal improvement in recipients of CVT donor cells.
Conclusions:
- Increased microbial exposure in SPF mice augments gut microbiota diversity and myeloid cell production.
- This exposure stimulates KSL cell reconstitution and alters hematopoietic gene expression.
- While hematopoietic stem cell reconstitution is enhanced, mature blood cell engraftment is not significantly improved.
