Molecular signatures of self-renewal, differentiation, and lineage choice in multipotential hemopoietic progenitor cells in vitro.
Heyworth, Clare M
AffiliationSection of Gene Function and Regulation, The Institute of Cancer Research, London SW3 6JB, UK.
MetadataShow full item record
AbstractThe molecular mechanisms governing self-renewal, differentiation, and lineage specification remain unknown. Transcriptional profiling is likely to provide insight into these processes but, as yet, has been confined to "static" molecular profiles of stem and progenitors cells. We now provide a comprehensive, statistically robust, and "dynamic" analysis of multipotent hemopoietic progenitor cells undergoing self-renewal in response to interleukin-3 (IL-3) and multilineage differentiation in response to lineage-affiliated cytokines. Cells undergoing IL-3-dependent proliferative self-renewal displayed striking complexity, including expression of genes associated with different lineage programs, suggesting a highly responsive compartment poised to rapidly execute intrinsically or extrinsically initiated cell fate decisions. A remarkable general feature of early differentiation was a resolution of complexity through the downregulation of gene expression. Although effector genes characteristic of mature cells were upregulated late, coincident with morphological changes, lineage-specific changes in gene expression were observed prior to this, identifying genes which may provide early harbingers of unilineage commitment. Of particular interest were genes that displayed differential behavior irrespective of the lineage elaborated, many of which were rapidly downregulated within 4 to 8 h after exposure to a differentiation cue. These are likely to include genes important in self-renewal, the maintenance of multipotentiality, or the negative regulation of differentiation per se.
CitationMolecular signatures of self-renewal, differentiation, and lineage choice in multipotential hemopoietic progenitor cells in vitro. 2004, 24 (2):741-56 Mol. Cell. Biol.
JournalMolecular and Cellular Biology
- Lhx2 expression promotes self-renewal of a distinct multipotential hematopoietic progenitor cell in embryonic stem cell-derived embryoid bodies.
- Authors: Dahl L, Richter K, Hägglund AC, Carlsson L
- Issue date: 2008 Apr 23
- Transient expression of PU.1 commits multipotent progenitors to a myeloid fate whereas continued expression favors macrophage over granulocyte differentiation.
- Authors: McIvor Z, Hein S, Fiegler H, Schroeder T, Stocking C, Just U, Cross M
- Issue date: 2003 Jan
- Gene expression analysis of purified hematopoietic stem cells and committed progenitors.
- Authors: Terskikh AV, Miyamoto T, Chang C, Diatchenko L, Weissman IL
- Issue date: 2003 Jul 1
- Gene coexpression analysis in single cells indicates lymphomyeloid copriming in short-term hematopoietic stem cells and multipotent progenitors.
- Authors: Gautreau L, Boudil A, Pasqualetto V, Skhiri L, Grandin L, Monteiro M, Jais JP, Ezine S
- Issue date: 2010 May 1
- Isolation of MYADM, a novel hematopoietic-associated marker gene expressed in multipotent progenitor cells and up-regulated during myeloid differentiation.
- Authors: Pettersson M, Dannaeus K, Nilsson K, Jönsson JI
- Issue date: 2000 Mar