The cell fate determinant Scribble is required for maintenance of hematopoietic stem cell function
Standard
The cell fate determinant Scribble is required for maintenance of hematopoietic stem cell function. / Mohr, Juliane; Dash, Banaja P; Schnoeder, Tina M; Wolleschak, Denise; Herzog, Carolin; Tubio Santamaria, Nuria; Weinert, Sönke; Godavarthy, Sonika; Zanetti, Costanza; Naumann, Michael; Hartleben, Björn; Huber, Tobias B; Krause, Daniela S; Kähne, Thilo; Bullinger, Lars; Heidel, Florian H.
In: LEUKEMIA, Vol. 32, No. 5, 05.2018, p. 1211-1221.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - The cell fate determinant Scribble is required for maintenance of hematopoietic stem cell function
AU - Mohr, Juliane
AU - Dash, Banaja P
AU - Schnoeder, Tina M
AU - Wolleschak, Denise
AU - Herzog, Carolin
AU - Tubio Santamaria, Nuria
AU - Weinert, Sönke
AU - Godavarthy, Sonika
AU - Zanetti, Costanza
AU - Naumann, Michael
AU - Hartleben, Björn
AU - Huber, Tobias B
AU - Krause, Daniela S
AU - Kähne, Thilo
AU - Bullinger, Lars
AU - Heidel, Florian H
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/s41375-018-0025-0
DO - 10.1038/s41375-018-0025-0
M3 - SCORING: Journal article
C2 - 29467485
VL - 32
SP - 1211
EP - 1221
JO - LEUKEMIA
JF - LEUKEMIA
SN - 0887-6924
IS - 5
ER -
