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A Regulatory network of microRNAs confers lineage commitment during early developmental trajectories of B and T lymphocytes.

ABSTRACT: The commitment of hematopoietic multipotent progenitors (MPPs) towards a particular lineage involves activation of cell-type-specific genes and silencing of genes that promote alternate cell fates. Although the gene expression programs of early-B and early-T lymphocyte development are mutually exclusive, we show these cell types exhibit significantly correlated microRNA profiles. However, their corresponding miRNA-targetomes are distinct and predominated by transcripts associated with NK, DC, and myeloid lineages, suggesting miRNAs function in a cell-autonomous manner. Combinatorial expression of microRNAs: miR-186-5p, miR-128-3p, and miR-330-5p in MPPs significantly attenuate their myeloid differentiation potential due to the repression of myeloid-associated transcripts. Depletion of these miRNAs caused a pronounced de-repression of myeloid lineage targets in differentiating early-B and early-T cells, resulting in a mixed-lineage gene expression pattern. De novo motif analysis combined with an assay of promoter activities indicate that B, as well as T lineage determinants, drive the expression of these miRNAs in lymphoid lineages. Collectively, we present a paradigm that miRNAs are conserved between developing B and T lymphocytes, yet they target distinct sets of promiscuously-expressed lineage-inappropriate genes to suppress alternate cell-fate options. Thus, our studies provide a comprehensive compendium of miRNAs with functional implications for B and T lymphocyte development.

ORGANISM(S): Mus musculus

PROVIDER: GSE153544 | GEO | 2021/10/08

REPOSITORIES: GEO

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A Regulatory network of microRNAs confers lineage commitment during early developmental trajectories of B and T lymphocytes.

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