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The SHB protein is required for efficient multilineage differentiation of mouse embryonic stem cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2003 (English)In: Exp Cell Res, Vol. 286, no (1), 40-56 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 286, no (1), 40-56 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-94469OAI: oai:DiVA.org:uu-94469DiVA: diva2:168326
Available from: 2006-05-10 Created: 2006-05-10 Last updated: 2012-12-17
In thesis
1. The Role of the SHB Adapter Protein in Cell Differentiation and Development
Open this publication in new window or tab >>The Role of the SHB Adapter Protein in Cell Differentiation and Development
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The present study was conducted in order to assess a role of the SH2 domain-containing adapter protein SHB in development and cell differentiation.

Embryonic stem (ES) cells overexpressing SHB and SHB with an inactive SH2 domain (R522K-SHB) were obtained. Microarray analysis in the SHB clone revealed altered expression of genes connected with neural cell function. The R522K-SHB clone exhibited altered expression of several transcription factors related to development. ES cells were differentiated by forming aggregates named embryoid bodies (EBs). The morphology of EBs was altered in the R522K-SHB clones, which showed fewer cavities. Expression of endodermal markers was decreased in the R522K-SHB EBs.

To further investigate the role of SHB in differentiation, murine ES cell lines deficient for one (SHB+/-) or both SHB alleles (SHB-/-) were generated. SHB deficient clones increased the expression of mesendodermal and endodermal markers and decreased expression of two receptors, VEGFR2 and FGFR1, connected with blood vessel differentiation. Similarly, blood vessels showed an altered morphology in SHB+/- and SHB-/- EBs after VEGF stimulation. SHB-/- ES cells also formed fewer blood colonies than control ES cells.

Finally, the role of the SHB adapter protein in vivo was analyzed by generating a SHB deficient mouse (SHB-/-). SHB-/- animals are viable, fertile, but suffer from leukopenia and anemia. SHB-/- animals demonstrate an abnormal morphology of blood vessels in the liver and kidney. Breeding of SHB+/- animals revealed an abnormal segregation of the mutant allele with an increased number of SHB+/- animals and a decreased number of SHB-/- and SHB+/+animals. Backcross analysis of SHB+/- females with SHB+/+ males displayed an increased number of SHB+/- offspring already at the blastocyst level. Simultaneously, embryos from SHB+/- mothers show an increased malformation rate in comparison to embryos from SHB+/+ mothers.

In summary, the study suggests a role of SHB in reproduction and development and in mesodermal and endodermal specification.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 46 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 150
Cell biology, SHB, transgene, ES cells, cavitation, knockout, mouse, vasculogenesis, hematopoiesis, endoderm, mesoderm, malformation, Cellbiologi
urn:nbn:se:uu:diva-6850 (URN)91-554-6562-5 (ISBN)
Public defence
2006-06-03, Room B21, Biomedical Center, Husargatan 3, Uppsala, 13:15
Available from: 2006-05-10 Created: 2006-05-10Bibliographically approved

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Anneren, CeciliaWelsh, Michael
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