DERARE RNA-seq
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE87556 | GEO | 2018/05/29
REPOSITORIES: GEO
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Project description:Purpose: The goal of this study is to compare NGS-derived transcriptome profiling (RNA-seq) of Ltbr-deficient and -proficient LT/ST-HSCs isolated from chimeric mice. Methods: Transcriptomic profiles of Ltbr-/- and Ly5.1 LT/ST-HSCs isolated from chimeric mice 6 weeks after reconstitution were assessed in triplicate by deep sequencing, using Illumina NextSeq 500. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: We mapped about 60 million sequence reads per sample to the mouse genome (GRCm38 - mm10) and identified expressed transcripts in Ltbr-/- and Ly5.1 LT/ST-HSCs isolated from chimeric mice. RNA-seq. data confirmed stable expression of known housekeeping genes. Differentially expressed genes between the Ltbr-/- and Ly5.1 LT/ST-HSCs were identified with a fold change ≥1.5 and FDR p-value <0.05. Conclusions: Our study represents the first detailed transcriptome analysis of Ltbr-deficient and -proficient LT/ST-HSCs, with biologic replicates, generated by RNA-seq. technology. Our results show that Ltbr signaling regulates HSC proliferation and differentiation. Evaluation of mRNA content in Ltbr-/- LT/ST-HSCs revealed that Ltbr-deficiency enhances HSC proliferation, differentiation, cell cycle and reduces the activity of canonical NFkB signaling.
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Project description:The hematopoietic stem cell (HSC) compartment is heterogeneous, yet our understanding of the identities of different HSC subtypes is limited. Here we show that platelet integrin CD41 (M-NM-1IIb), currently thought to only transiently mark fetal HSCs, is expressed on an adult HSC subtype that accumulates with age. CD41+ HSCs were largely quiescent and exhibited myeloerythroid and megakaryocyte gene priming, governed by Gata1, whereas CD41- HSCs were more proliferative and exhibited lymphoid gene priming. When isolated without the use of blocking antibodies, CD41+ HSCs possessed long-term repopulation capacity upon serial transplantations and showed a marked myeloid-bias compared to CD41-HSCs, which yielded a more lymphoid-biased progeny. CD41-knockout mice displayed multilineage hematopoietic defects coupled with decreased quiescence and survival of HSCs, suggesting that CD41 is functionally relevant for HSC maintenance and hematopoietic homeostasis. Transplantation experiments indicated that CD41-KO associated defects are long-term transplantable and HSC-derived, and in part mediated through the loss of platelet mass leading to decreases in HSC exposure to important platelet released cytokines, such as TGFM-NM-21. In summary, our data provide a novel marker to identify a myeloid-biased HSC subtype that becomes prevalent with age, and highlights the dogma of HSC regulation by their progeny. For microarray analysis, 1000 HSCs were FACS sorted from pools of 4-5 mice directly into lysis buffer, RNA extracted and whole transcript amplification was performed as previously described (Gonzalez-Roca E, Garcia-Albeniz X, Rodriguez-Mulero S, Gomis RR, Kornacker K, Auer H. Accurate expression profiling of very small cell populations. PLoS One. 2010;5:e14418.)
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