Dysregulated microRNA Activity in Shwachman-Diamond Syndrome
Abstract
Shwachman-Diamond Syndrome (SDS) is an inherited bone marrow failure primarily affecting myeloid development. Because the affected cells are rare and heterogeneous, the altered genetic networks in vivo remain unknown. The central goal of this grant is to define transcriptional signatures of bone marrow failure in SDS using single cell RNA-seq of patient cells. We will analyze these datasets to test the novel hypothesis that reduced microRNA activity contributes to hematopoietic dysfunction in SDS. To date, we have sequenced ~300 hematopoietic stem and progenitor cells (HSPC) from normal donors and SDS patients and established, to our knowledge, the first lineage maps of early hematopoiesis at single cell resolution. We have used single cell statistical frameworks such as MAST, SCDE and WGCNA to identify SDS-specific gene expression patterns that are common to all HSPC or restricted to particular lineages. Ongoing and future work includes 1) annotation of differentially expressed genes to hematopoietic phenotypes in cellular and animal models of SDS, 2) profiling thousands more HSPC using high-throughput Drop-seq, and 3) generation of microRNA expression profiles from HSPCs to be overlaid onto mRNA profiles.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1032889
Entities
People
- Carl Novina
Organizations
- Dana–Farber Cancer Institute