Mis-expression of GATA6 re-programs cell fate during early hematopoiesis
- Author(s)
- Audiger, C; Laâbi, Y; Nie, J; Gibson, L; Wilson-Annan, J; Brook-Carter, P; Kueh, A; Harris, AW; Naik, S; Nutt, SL; Strasser, A; Adams, JM; Bouillet, P; Chopin, M;
- Details
- Publication Year 2024-04-26,Volume 43,Issue #5,Page 114159
- Journal Title
- Cell Reports
- Abstract
- The traditional view of hematopoiesis is that myeloid cells derive from a common myeloid progenitor (CMP), whereas all lymphoid cell populations, including B, T, and natural killer (NK) cells and possibly plasmacytoid dendritic cells (pDCs), arise from a common lymphoid progenitor (CLP). In Max41 transgenic mice, nearly all B cells seem to be diverted into the granulocyte lineage. Here, we show that these mice have an excess of myeloid progenitors, but their CLP compartment is ablated, and they have few pDCs. Nevertheless, T cell and NK cell development proceeds relatively normally. These hematopoietic abnormalities result from aberrant expression of Gata6 due to serendipitous insertion of the transgene enhancer (Eμ) in its proximity. Gata6 mis-expression in Max41 transgenic progenitors promoted the gene-regulatory networks that drive myelopoiesis through increasing expression of key transcription factors, including PU.1 and C/EBPa. Thus, mis-expression of a single key regulator like GATA6 can dramatically re-program multiple aspects of hematopoiesis.
- Keywords
- CP: Developmental biology; Eμ enhancer; GATA transcription factors; NK cells; T cells; common lymphoid progenitors; hematopoiesis; lineage deviation; plasmacytoid dendritic cells
- Research Division(s)
- Immunology; Blood Cells And Blood Cancer; Infectious Diseases And Immune Defence
- PubMed ID
- 38676923
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2024.114159
- Open Access at Publisher's Site
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Creation Date: 2024-05-08 10:06:32
Last Modified: 2024-05-08 10:17:41