Single-cell characterization of haematopoietic progenitors and their trajectories in homeostasis and perturbed haematopoiesis.
Amir GiladiFranziska PaulYoni HerzogYaniv LublingAssaf WeinerIdo YofeDiego JaitinNina Cabezas-WallscheidRegine DressFlorent GinhouxAndreas TrumppAmos TanayAmir GiladiPublished in: Nature cell biology (2018)
The dynamics of haematopoietic stem cell differentiation and the hierarchy of oligopotent stem cells in the bone marrow remain controversial. Here we dissect haematopoietic progenitor populations at single cell resolution, deriving an unbiased reference model of transcriptional states in normal and perturbed murine bone marrow. We define the signature of the naive haematopoietic stem cell and find a continuum of core progenitor states. Core cell populations mix transcription of pre-myeloid and pre-lymphoid programs, but do not mix erythroid or megakaryocyte programs with other fates. CRISP-seq perturbation analysis confirms our models and reveals that Cebpa regulates entry into all myeloid fates, while Irf8 and PU.1 deficiency block later differentiation towards monocyte or granulocyte fates. Our transcriptional map defines a reference network model for blood progenitors and their differentiation trajectories during normal and perturbed haematopoiesis.
Keyphrases
- single cell
- bone marrow
- stem cells
- rna seq
- dendritic cells
- transcription factor
- high throughput
- mesenchymal stem cells
- public health
- gene expression
- depressive symptoms
- cell therapy
- acute myeloid leukemia
- hiv infected
- oxidative stress
- heat shock
- genetic diversity
- replacement therapy
- genome wide
- cell fate
- recombinant human
- heat shock protein