Abstract
Transcriptional regulatory networks (TRN) control the underlying mechanisms behind cellular functions and they are defined by a set of core transcription factors regulating cascades of peripheral genes. Here we report SPI1, CEBPA, MNDA and IRF8 as core transcription factors of monocyte TRN and demonstrate functional inductions of phagocytosis, inflammatory response and chemotaxis activities in human dermal fibroblasts. The Gene Ontology and KEGG pathway analyses also revealed notable representation of genes involved in immune response and endocytosis in fibroblasts. Moreover, monocyte TRN-inducers triggered multiple monocyte-specific genes based on the transcription factor motif response analysis and suggest that complex cellular TRNs are uniquely amenable to elicit cell-specific functions in unrelated cell types.
Highlights
A transcriptional regulatory network (TRN), in part, defines the functional properties of a cell-type [1]
We carried out a gene expression profiling together with literature-based text mining in order to isolate a broader set of monocyte core TRN elements
We have found that key biological functions of monocytes can be accompanied in human dermal fibroblasts
Summary
A transcriptional regulatory network (TRN), in part, defines the functional properties of a cell-type [1]. The ability to reengineer cellular TRNs would provide vast opportunities to treat patients suffering from impaired function of physiologically important cell types such as pancreatic b-cells [2]. Does not project a natural biological process, and approaches to identify a set of defined factors often deemed hit-ormiss or lack supporting evidence for selecting the candidate genes to induce reprogramming. It is unknown whether every cell type can be reprogrammed. Cells reengineered to implement cell-specific function(s) would be of great value since rectifying a specific cellular function is often preferred compared to a complete replacement of impaired cells [9]
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