The phosphatases STS1 and STS2 regulate hematopoietic stem and progenitor cell fitness

Jing Zhang; Olesya Vakhrusheva; Srinivasa Rao Bandi; Özlem Demirel; Julhash U. Kazi; Ramona Gomes Fernandes; Katja Jakobi; Astrid Eichler; Lars Rönnstrand; Michael A. Rieger; Nick Carpino; Hubert Serve; Christian H. Brandts

doi:10.1016/j.stemcr.2015.08.006

The phosphatases STS1 and STS2 regulate hematopoietic stem and progenitor cell fitness

Jing Zhang
, Olesya Vakhrusheva
, Srinivasa Rao Bandi
, Özlem Demirel
, Julhash U. Kazi
, Ramona Gomes Fernandes
, Katja Jakobi
, Astrid Eichler
, Lars Rönnstrand
, Michael A. Rieger
, Nick Carpino
, Hubert Serve
, Christian H. Brandts

Microbiology and Immunology

Goethe University Frankfurt
German Cancer Research Center
Lund University

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

FLT3 and c-KIT are crucial regulators of hematopoietic stem and progenitor cells. We investigated the role of STS1 and STS2 on FLT3 and c-KIT phosphorylation, activity, and function in normal and stress-induced hematopoiesis. STS1/STS2-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity. Although long-term hematopoietic stem cells are not increased in numbers, lack of STS1 and STS2 significantly promotes long-term repopulation activity, demonstrating a pivotal role of STS1/STS2 in regulating hematopoietic stem and progenitor cell fitness. Biochemical analysis identified STS1/STS2 as direct phosphatases of FLT3 and c-KIT. Loss of STS1/STS2 induces hyperphosphorylation of FLT3, enhances AKT signaling, and confers a strong proliferative advantage. Therefore, our study reveals that STS1 and STS2 may serve as novel pharmaceutical targets to improve hematopoietic recovery after bone marrow transplantation.

Original language	English
Pages (from-to)	633-646
Number of pages	14
Journal	Stem Cell Reports
Volume	5
Issue number	4
DOIs	https://doi.org/10.1016/j.stemcr.2015.08.006
State	Published - Oct 13 2015

Access to Document

10.1016/j.stemcr.2015.08.006

Cite this

@article{6257f4f41e484f02aebdf6cc2a280f4d,

title = "The phosphatases STS1 and STS2 regulate hematopoietic stem and progenitor cell fitness",

abstract = "FLT3 and c-KIT are crucial regulators of hematopoietic stem and progenitor cells. We investigated the role of STS1 and STS2 on FLT3 and c-KIT phosphorylation, activity, and function in normal and stress-induced hematopoiesis. STS1/STS2-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity. Although long-term hematopoietic stem cells are not increased in numbers, lack of STS1 and STS2 significantly promotes long-term repopulation activity, demonstrating a pivotal role of STS1/STS2 in regulating hematopoietic stem and progenitor cell fitness. Biochemical analysis identified STS1/STS2 as direct phosphatases of FLT3 and c-KIT. Loss of STS1/STS2 induces hyperphosphorylation of FLT3, enhances AKT signaling, and confers a strong proliferative advantage. Therefore, our study reveals that STS1 and STS2 may serve as novel pharmaceutical targets to improve hematopoietic recovery after bone marrow transplantation.",

author = "Jing Zhang and Olesya Vakhrusheva and Bandi, \{Srinivasa Rao\} and {\"O}zlem Demirel and Kazi, \{Julhash U.\} and Fernandes, \{Ramona Gomes\} and Katja Jakobi and Astrid Eichler and Lars R{\"o}nnstrand and Rieger, \{Michael A.\} and Nick Carpino and Hubert Serve and Brandts, \{Christian H.\}",

note = "Publisher Copyright: {\textcopyright} 2015 The Authors.",

year = "2015",

month = oct,

day = "13",

doi = "10.1016/j.stemcr.2015.08.006",

language = "English",

volume = "5",

pages = "633--646",

journal = "Stem Cell Reports",

issn = "2213-6711",

number = "4",

}

TY - JOUR

T1 - The phosphatases STS1 and STS2 regulate hematopoietic stem and progenitor cell fitness

AU - Zhang, Jing

AU - Vakhrusheva, Olesya

AU - Bandi, Srinivasa Rao

AU - Demirel, Özlem

AU - Kazi, Julhash U.

AU - Fernandes, Ramona Gomes

AU - Jakobi, Katja

AU - Eichler, Astrid

AU - Rönnstrand, Lars

AU - Rieger, Michael A.

AU - Carpino, Nick

AU - Serve, Hubert

AU - Brandts, Christian H.

PY - 2015/10/13

Y1 - 2015/10/13

N2 - FLT3 and c-KIT are crucial regulators of hematopoietic stem and progenitor cells. We investigated the role of STS1 and STS2 on FLT3 and c-KIT phosphorylation, activity, and function in normal and stress-induced hematopoiesis. STS1/STS2-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity. Although long-term hematopoietic stem cells are not increased in numbers, lack of STS1 and STS2 significantly promotes long-term repopulation activity, demonstrating a pivotal role of STS1/STS2 in regulating hematopoietic stem and progenitor cell fitness. Biochemical analysis identified STS1/STS2 as direct phosphatases of FLT3 and c-KIT. Loss of STS1/STS2 induces hyperphosphorylation of FLT3, enhances AKT signaling, and confers a strong proliferative advantage. Therefore, our study reveals that STS1 and STS2 may serve as novel pharmaceutical targets to improve hematopoietic recovery after bone marrow transplantation.

AB - FLT3 and c-KIT are crucial regulators of hematopoietic stem and progenitor cells. We investigated the role of STS1 and STS2 on FLT3 and c-KIT phosphorylation, activity, and function in normal and stress-induced hematopoiesis. STS1/STS2-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity. Although long-term hematopoietic stem cells are not increased in numbers, lack of STS1 and STS2 significantly promotes long-term repopulation activity, demonstrating a pivotal role of STS1/STS2 in regulating hematopoietic stem and progenitor cell fitness. Biochemical analysis identified STS1/STS2 as direct phosphatases of FLT3 and c-KIT. Loss of STS1/STS2 induces hyperphosphorylation of FLT3, enhances AKT signaling, and confers a strong proliferative advantage. Therefore, our study reveals that STS1 and STS2 may serve as novel pharmaceutical targets to improve hematopoietic recovery after bone marrow transplantation.

UR - https://www.scopus.com/pages/publications/84944441375

U2 - 10.1016/j.stemcr.2015.08.006

DO - 10.1016/j.stemcr.2015.08.006

M3 - Article

C2 - 26365512

AN - SCOPUS:84944441375

SN - 2213-6711

VL - 5

SP - 633

EP - 646

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 4

ER -

The phosphatases STS1 and STS2 regulate hematopoietic stem and progenitor cell fitness

Abstract

Access to Document

Other files and links

Fingerprint

Cite this