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Hematopoietic Transcriptional Comparison of HSC from B10.BR/JRep and B10.BR/J (drifted) mice

ABSTRACT: Divergence has occured between the B10.BR-H2k H2-T18a/SgSnJJrep and B10.BR-H2k H2-T18a/SgSnJ (drifted) mouse strains, resulting in altered antigenic recognition and differential bone marrow engraftment capability. The microarray data demonstrate that the transcriptional profile of genes associated with hematopoiesis differs between lineage negative (as a marker for hematopoietic stem cells) bone marrow cells isolated from the B10.BR-H2k H2-T18a/SgSnJJrep and B10.BR-H2k H2-T18a/SgSnJ (drifted) mouse strains.

ORGANISM(S): Mus musculus

PROVIDER: GSE17471 | GEO | 2009/09/16

SECONDARY ACCESSION(S): PRJNA118713

REPOSITORIES: GEO

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Hematopoietic Transcriptional Comparison of HSC from B10.BR/JRep and B10.BR/J (drifted) mice

Project description:Divergence has occured between the B10.BR-H2k H2-T18a/SgSnJJrep and B10.BR-H2k H2-T18a/SgSnJ (drifted) mouse strains, resulting in altered antigenic recognition and differential bone marrow engraftment capability. The microarray data demonstrate that the transcriptional profile of genes associated with hematopoiesis differs between lineage negative (as a marker for hematopoietic stem cells) bone marrow cells isolated from the B10.BR-H2k H2-T18a/SgSnJJrep and B10.BR-H2k H2-T18a/SgSnJ (drifted) mouse strains. Bone marrow cells from ten male mice of each strain, aged 10-12 weeks, were harvested. One pooled sample was analyzed for each strain.

2009-09-15 | E-GEOD-17471 | biostudies-arrayexpress

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Project description:To identify novel mechanisms regulating allogeneic hematopoietic cell engraftment, we previously used a forward genetic approach and described identification, in mice, of the Bmgr5 bone marrow (BM) engraftment quantitative trait locus (QTL). This QTL confers dominant and large allele effects for engraftment susceptibility. It was localized to chromosome 16 by classical quantitative genetic techniques in a segregating backcross bred from susceptible BALB.K and resistant B10.BR mice. We now report verification of the Bmgr5 QTL using reciprocal chromosome 16 consomic strains. The BM engraftment phenotype in these consomic mice shows that Bmgr5 susceptibility alleles are not only sufficient but also indispensable for conferring permissiveness for allogeneic BM engraftment. Using panels of congenic mice, we resolved the Bmgr5 QTL into two separate subloci, termed Bmgr5a and Bmgr5b, each conferring permissiveness for the engraftment phenotype and both fine mapped to an interval amenable to positional cloning. Candidate Bmgr5 genes were then prioritized using whole exome DNA sequencing and microarray gene expression profiling. Further studies are needed to elucidate the genetic interaction between Bmgr5a and Bmgr5b and identify causative genes and underlying gene variants. This may lead to new approaches for overcoming the problem of graft rejection in clinical hematopoietic cell transplantation. B10.BALBChr16 and BALB.B10Chr16 consomic strain mice were constructed in our laboratory for validation of bone marrow engraftment and graft-vs-host diseaes QTLs. The parental strains for consomic line construction were B10.BR (B10.BR-H2k H2-T18a/SgSnJJrep) and BALB.K (C.C3-H2k/LilMcdJ). The JAX Mouse Diveristy 620K SNP Array was used to verify adequate removal of residual background heterozygosity. Liver DNA was delivered to JAX Mouse Diversity Genotyping Array Service (Jackson Laboratory) for the SNP Array genotyping.

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Mus musculus strain:BALB.K and B10.BR

Project description:Mus musculus strain:BALB.K and B10.BR Exome

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Project description:B10.BR mice were lethally irradiated and infused with 5000 FACS-sorted HSCs and 1000000 T cells from C57B/6J donors with 50000 FACS-purified wild-type pDCs or VIP-KO pDCs. On day 8 and day 15 after the bone marrow transplant, donor T cells were isolated and the RNA expression were detected.

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