Immune Netw.  2015 Oct;15(5):252-259. 10.4110/in.2015.15.5.252.

Altered Gut Microbiota Composition in Rag1-deficient Mice Contributes to Modulating Homeostasis of Hematopoietic Stem and Progenitor Cells

• Kwon O
• Lee S
• Kim JH
• Kim H
• Lee SW

• KMID: 2150854
• DOI: http://doi.org/10.4110/in.2015.15.5.252

Abstract

Hematopoietic stem and progenitor cells (HSPCs) can produce all kind of blood lineage cells, and gut microbiota that consists of various species of microbe affects development and maturation of the host immune system including gut lymphoid cells and tissues. However, the effect of altered gut microbiota composition on homeostasis of HSPCs remains unclear. Here we show that compositional change of gut microbiota affects homeostasis of HSPCs using Rag1(-/-) mice which represent lymphopenic condition. The number and proportions of HSPCs in Rag1(-/-) mice are lower compared to those of wild types. However, the number and proportions of HSPCs in Rag1(-/-) mice are restored as the level of wild types through alteration of gut microbiota diversity via transferring feces from wild types. Gut microbiota composition of Rag1(-/-) mice treated with feces from wild types shows larger proportions of family Prevotellaceae and Helicobacterceae whereas lower proportions of family Lachnospiraceae compared to unmanipulated Rag1(-/-) mice. In conclusion, gut microbiota composition of lymphopenic Rag1(-/-) mice is different to that of wild type, which may lead to altered homeostasis of HSPCs.

Keyword

Hematopoietic stem and progenitor cells; gut microbiota; lymphopenic state

MeSH Terms

Animals
Feces
Homeostasis*
Humans
Immune System
Lymphocytes
Mice*
Microbiota*
Stem Cells*

Figure

• 

  Figure 1 Lymphopenic condition reduces the number of HSPCs. (A) Absolute number of total bone marrow (BM) cells from wild type and Rag1-/- mice. (B) Flow cytometry of LSK cells (Lin- Sca-1+ c-Kit+) and MPs (Lin- Sca-1- c-Kit+), and LT-HSCs (Lin- Sca-1+ c-Kit+ CD150+ CD48-), ST- HSCs (Lin- Sca-1+ c-Kit+ CD150+ CD48+), and MPPs (Lin- Sca-1+ c-Kit+ CD150- CD48+). Absolute number (C) and the frequency (D) of LSK cells, MPs, LT-HSCs, ST-HSCs, and MPPs among total BM cells. (E) The percentage of LT-HSCs, ST-HSCs and MPPs among LSK cells. Mean values±s.e.m. are shown. *p<0.05, **p<0.01, ***p<0.001, compared with drinking water controls. (Student's t-test).

• 

  Figure 2 Feces delivery restores the number and proportion of HSCs in Rag1-/- mice. (A) Experimental scheme. (B) Absolute number of total BM cells from the mice groups. Absolute number (C) and the percentage (D) of LSK cells, MPs, LT-HSCs, ST-HSCs, and MPPs among total BM cells. (E) The percentage of LT-HSCs, ST-HSCs and MPPs among LSK cells. Mean values±s.e.m. are shown. *p<0.05, **p<0.01, ***p<0.001, compared with drinking water controls. (Student's t-test).

• 

  Figure 3 Feces delivery alters composition of colon microbial community. (A) Experimental scheme for metagenomics analysis. Gut microbiota composition based on phylum (A), family (B), and species (C) by bacterial DNA metagenomics analysis. Bacterial DNA in pooled feces (from 4 to 5 mice per each group) were identified by standard microbiological method.

• 

  Figure 4 Colonization of H. muridarum has no effect on HSCs of Rag1-/- mice. (A) Experimental scheme. (B) Absolute number of total BM cells from the mice groups. Absolute number (C) and the percentage (D) of LSK cells, MPs, LT-HSCs, ST-HSCs, and MPPs among total BM cells. (E) The percentage of LT-HSCs, ST-HSCs and MPPs among LSK cells. Mean values±s.e.m. are shown. *p<0.05, compared with drinking water controls. (Student's t-test).

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