The cell fate determinant Scribble is required for maintenance of hematopoietic stem cell function

Item Type:	Article
Title:	The cell fate determinant Scribble is required for maintenance of hematopoietic stem cell function
Creators Name:	Mohr, J. and Dash, B.P. and Schnoeder, T.M. and Wolleschak, D. and Herzog, C. and Tubio Santamaria, N. and Weinert, S. and Godavarthy, S. and Zanetti, C. and Naumann, M. and Hartleben, B. and Huber, T.B. and Krause, D.S. and Kähne, T. and Bullinger, L. and Heidel, F.H.
Abstract:	Cell fate determinants influence self-renewal potential of hematopoietic stem cells. Scribble and Llgl1 belong to the Scribble polarity complex and reveal tumor-suppressor function in drosophila. In hematopoietic cells, genetic inactivation of Llgl1 leads to expansion of the stem cell pool and increases self-renewal capacity without conferring malignant transformation. Here we show that genetic inactivation of its putative complex partner Scribble results in functional impairment of hematopoietic stem cells (HSC) over serial transplantation and during stress. Although loss of Scribble deregulates transcriptional downstream effectors involved in stem cell proliferation, cell signaling, and cell motility, these effectors do not overlap with transcriptional targets of Llgl1. Binding partner analysis of Scribble in hematopoietic cells using affinity purification followed by mass spectometry confirms its role in cell signaling and motility but not for binding to polarity modules described in drosophila. Finally, requirement of Scribble for self-renewal capacity also affects leukemia stem cell function. Thus, Scribble is a regulator of adult HSCs, essential for maintenance of HSCs during phases of cell stress.
Keywords:	Acute Myeloid Leukemia, Haematopoietic Stem Cells, Animals, Drosophila
Source:	Leukemia
ISSN:	1476-5551
Publisher:	Nature Publishing Group
Volume:	32
Number:	5
Page Range:	1211-1221
Date:	May 2018
Official Publication:	https://doi.org/10.1038/s41375-018-0025-0
PubMed:	View item in PubMed

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