Single-Cell Network Analysis Identifies DDIT3 as a Nodal Lineage Regulator in Hematopoiesis.

Summary, in English

We explore cell heterogeneity during spontaneous and transcription-factor-driven commitment for network inference in hematopoiesis. Since individual genes display discrete OFF states or a distribution of ON levels, we compute and combine pairwise gene associations from binary and continuous components of gene expression in single cells. Ddit3 emerges as a regulatory node with positive linkage to erythroid regulators and negative association with myeloid determinants. Ddit3 loss impairs erythroid colony output from multipotent cells, while forcing Ddit3 in granulo-monocytic progenitors (GMPs) enhances self-renewal and impedes differentiation. Network analysis of Ddit3-transduced GMPs reveals uncoupling of myeloid networks and strengthening of erythroid linkages. RNA sequencing suggests that Ddit3 acts through development or stabilization of a precursor upstream of GMPs with inherent Meg-E potential. The enrichment of Gata2 target genes in Ddit3-dependent transcriptional responses suggests that Ddit3 functions in an erythroid transcriptional network nucleated by Gata2.

• Author: Cristina Pina; José Teles; Cristina Fugazza; Gillian May; Dapeng Wang; Yanping Guo; Shamit Soneji; John Brown; Patrik Edén; Mattias Ohlsson; Carsten Peterson; Tariq Enver
• Department/s: Computational Biology and Biological Physics - Undergoing reorganization; StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
• Publishing year: 2015
• Language: English
• Pages: 1503-1510
• Publication/Series: Cell Reports
• Volume: 11
• Issue: 10
• Full text: - 3 MB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/26051941?dopt=Abstract; http://dx.doi.org/10.1016/j.celrep.2015.05.016
• Document type: Journal article
• Publisher: Cell Press
• Topic: Hematology
• Status: Published
• ISBN/ISSN/Other: ISSN: 2211-1247