Loss of Survivin in Intestinal Epithelial Progenitor Cells Leads to Mitotic Catastrophe and Breakdown of Gut Immune Homeostasis

Martini E, Wittkopf N, Günther C, Leppkes M, Okada H, Watson AJ, Podstawa E, Backert I, Amann KU, Neurath M, Becker C (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 14

Pages Range: 1062-73

Journal Issue: 5

DOI: 10.1016/j.celrep.2016.01.010

Abstract

A tightly regulated balance of proliferation and cell death of intestinal epithelial cells (IECs) is essential for maintenance of gut homeostasis. Survivin is highly expressed during embryogenesis and in several cancer types, but little is known about its role in adult gut tissue. Here, we show that Survivin is specifically expressed in transit-amplifying cells and Lgr5(+) stem cells. Genetic loss of Survivin in IECs resulted in destruction of intestinal integrity, mucosal inflammation, and death of the animals. Survivin deletion was associated with decreased epithelial proliferation due to defective chromosomal segregation. Moreover, Survivin-deficient animals showed induced phosphorylation of p53 and H2AX and increased levels of cell-intrinsic apoptosis in IECs. Consequently, induced deletion of Survivin in Lgr5(+) stem cells led to cell death. In summary, Survivin is a key regulator of gut tissue integrity by regulating epithelial homeostasis in the stem cell niche.

Authors with CRIS profile

Eva Liebing Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Claudia Günther Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Ingo Backert Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Kerstin Ute Amann Department of Nephropathology Markus Neurath Lehrstuhl für Innere Medizin I Christoph Becker Professur für Molekulare Gastroenterologie

Involved external institutions

Kindai University / 近畿大学 JP Japan (JP) University of East Anglia GB United Kingdom (GB)

How to cite

APA:

Martini, E., Wittkopf, N., Günther, C., Leppkes, M., Okada, H., Watson, A.J.,... Becker, C. (2016). Loss of Survivin in Intestinal Epithelial Progenitor Cells Leads to Mitotic Catastrophe and Breakdown of Gut Immune Homeostasis. Cell Reports, 14(5), 1062-73. https://doi.org/10.1016/j.celrep.2016.01.010

MLA:

Martini, Eva, et al. "Loss of Survivin in Intestinal Epithelial Progenitor Cells Leads to Mitotic Catastrophe and Breakdown of Gut Immune Homeostasis." Cell Reports 14.5 (2016): 1062-73.

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