A recessive screen for genes regulating hematopoietic stem cells

Papathanasiou, Peter, Tunningley, Robert, Pattabiraman, Diwakar R., Ye, Ping, Gonda, Thomas J., Whittle, Belinda, Hamilton, Adam E., Cridland, Simon O., Lourie, Rohan and Perkins, Andrew C. (2010) A recessive screen for genes regulating hematopoietic stem cells. Blood, 116 26: 5849-5858. doi:10.1182/blood-2010-04-269951


Author Papathanasiou, Peter
Tunningley, Robert
Pattabiraman, Diwakar R.
Ye, Ping
Gonda, Thomas J.
Whittle, Belinda
Hamilton, Adam E.
Cridland, Simon O.
Lourie, Rohan
Perkins, Andrew C.
Title A recessive screen for genes regulating hematopoietic stem cells
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2010-12-23
Sub-type Article (original research)
DOI 10.1182/blood-2010-04-269951
Open Access Status
Volume 116
Issue 26
Start page 5849
End page 5858
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Collection year 2011
Language eng
Formatted abstract
Identification of genes that regulate the development, self-renewal, and differentiation of stem cells is of vital importance for understanding normal organogenesis and cancer; such knowledge also underpins regenerative medicine. Here we demonstrate that chemical mutagenesis of mice combined with advances in hematopoietic stem cell reagents and genome resources can efficiently recover recessive mutations and identify genes essential for generation and proliferation of definitive hematopoietic stem cells and/or their progeny. We used high-throughput fluorescence-activated cell sorter to analyze 9 subsets of blood stem cells, progenitor cells, circulating red cells, and platelets in more than 1300 mouse embryos at embryonic day (E) 14.5. From 45 pedigrees, we recovered 6 strains with defects in definitive hematopoiesis. We demonstrate rapid identification of a novel mutation in the c-Myb transcription factor that results in thrombocythemia and myelofibrosis as proof of principal of the utility of our fluorescence-activated cell sorter–based screen. Such phenotype-driven approaches will provide new knowledge of the genes, protein interactions, and regulatory networks that underpin stem cell biology.
Keyword Term reconstituting subset
ENU-mutagenesis
Transcription factor
c-Myb
Definitive hematopoiesis
Primitive erythroblasts
Myeloid metaplasia
Point mutation
Mpl(-/-) mice
Self-renewal
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Sun, 30 Jan 2011, 00:06:50 EST