Zeb1 Modulates Hematopoietic Stem Cell Fates Required for Suppressing Acute Myeloid Leukemia
The Journal of Clinical Investigation RESEARCH ARTICLE Zeb1 modulates hematopoietic stem cell fates required for suppressing acute myeloid leukemia Alhomidi Almotiri,1,2 Hamed Alzahrani,1 Juan Bautista Menendez-Gonzalez,1 Ali Abdelfattah,1 Badi Alotaibi,1 Lubaid Saleh,1 Adelle Greene,1 Mia Georgiou,1 Alex Gibbs,1 Amani Alsayari,1 Sarab Taha,1 Leigh-anne Thomas,1 Dhruv Shah,1, Sarah Edkins,3 Peter Giles,3 Marc P. Stemmler,4 Simone Brabletz,4 Thomas Brabletz,4 Ashleigh S. Boyd,5,6 Florian A. Siebzehnrubl,1 and Neil P. Rodrigues1 1European Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, United Kingdom. 2College of Applied Medical Sciences-Dawadmi, Shaqra University, Dawadmi, Saudi Arabia. 3Wales Gene Park and Wales Cancer Research Centre, Division of Cancer and Genetics, Cardiff University, School of Medicine, Cardiff, United Kingdom. 4Department of Experimental Medicine 1, Nikolaus- Fiebiger-Center for Molecular Medicine, FAU University Erlangen-Nürnberg, Erlangen, Germany. 5Department of Surgical Biotechnology, Division of Surgery and Interventional Science, Royal Free Hospital, and 6Institute of Immunity and Transplantation, University College London, London, United Kingdom. Zeb1, a zinc finger E-box binding homeobox epithelial-mesenchymal transition (EMT) transcription factor, confers properties of “stemness,” such as self-renewal, in cancer. Yet little is known about the function of Zeb1 in adult stem cells. Here, we used the hematopoietic system as a well-established paradigm of stem cell biology to evaluate Zeb1-mediated regulation of adult stem cells. We employed a conditional genetic approach using the Mx1-Cre system to specifically knock out (KO) Zeb1 in adult hematopoietic stem cells (HSCs) and their downstream progeny.
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