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Mattias Ohlsson

Mattias Ohlsson

Professor

Mattias Ohlsson

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

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

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.

Department/s

  • Computational Biology and Biological Physics
  • 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

Document type

Journal article

Publisher

Cell Press

Topic

  • Hematology

Status

Published

ISBN/ISSN/Other

  • ISSN: 2211-1247