Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis

Heather K Bone, Melanie J Welham

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Phosphoinositide 3-kinase (PI3K)-dependent signalling regulates a wide variety of cellular functions including proliferation and differentiation. Disruption of class I-A PI3K isoforms has implicated PI3K- mediated signalling in development of the early embryo and lymphohaemopoietic system. We have used embryonic stem (ES) cells as an in vitro model to study the involvement of PI3K-dependent signalling during early development and haemopoiesis. Both pharmacological inhibition and genetic manipulation of PI3K-dependent signalling demonstrate that PI3K-mediated signals, most likely via 3-phosphoinositide-dependent protein kinase 1 (PDK1), are required for proliferation of cells within developing embryoid bodies ( EBs). Surprisingly, the haemopoietic potential of EB-derived cells was not blocked upon PI3K inhibition but rather enhanced, correlating with modest increases in expression of haemopoietic marker genes. By contrast, PDK1-deficient EB-derived progeny failed to generate terminally differentiated haemopoietic lineages. This deficiency appeared to be due to a requirement for PI3K signalling during the proliferative phase of blast-colony-forming cell (BL-CFC) expansion, rather than as a result of effects on differentiation per se. We also demonstrate that PI3K-dependent signalling is required for optimal generation of erythroid and myeloid progenitors and their differentiation into mature haemopoietic colony types. These data demonstrate that PI3K- dependent signals play important roles at different stages of haemopoietic development.
Original languageEnglish
Pages (from-to)1752-1762
Number of pages11
JournalJournal of Cell Science
Volume120
Issue number10
DOIs
Publication statusPublished - 2007

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1-Phosphatidylinositol 4-Kinase
Embryoid Bodies
3-Phosphoinositide-Dependent Protein Kinases
Blast Crisis
Embryonic Stem Cells
Embryonic Development
Protein Isoforms
Cell Proliferation
Pharmacology

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Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis. / Bone, Heather K; Welham, Melanie J.

In: Journal of Cell Science, Vol. 120, No. 10, 2007, p. 1752-1762.

Research output: Contribution to journalArticle

Bone, Heather K ; Welham, Melanie J. / Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis. In: Journal of Cell Science. 2007 ; Vol. 120, No. 10. pp. 1752-1762.
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