CLASP2 safeguards hematopoietic stem cell properties during mouse and fish development

TY - JOUR

T1 - CLASP2 safeguards hematopoietic stem cell properties during mouse and fish development

AU - Klaus, Anna

AU - Clapes, Thomas

AU - Yvernogeau, Laurent

AU - Basu, Sreya

AU - Weijts, Bart

AU - Maas, Joris

AU - Smal, Ihor

AU - Galjart, Niels

AU - Robin, Catherine

N1 - Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2022/6/14

Y1 - 2022/6/14

N2 - Hematopoietic stem cells (HSCs) express a large variety of cell surface receptors that are associated with acquisition of self-renewal and multipotent properties. Correct expression of these receptors depends on a delicate balance between cell surface trafficking, recycling, and degradation and is controlled by the microtubule network and Golgi apparatus, whose roles have hardly been explored during embryonic/fetal hematopoiesis. Here we show that, in the absence of CLASP2, a microtubule-associated protein, the overall production of HSCs is reduced, and the produced HSCs fail to self-renew and maintain their stemness throughout mouse and zebrafish development. This phenotype can be attributed to decreased cell surface expression of the hematopoietic receptor c-Kit, which originates from increased lysosomal degradation in combination with a reduction in trafficking to the plasma membrane. A dysfunctional Golgi apparatus in CLASP2-deficient HSCs seems to be the underlying cause of the c-Kit expression and signaling imbalance.

AB - Hematopoietic stem cells (HSCs) express a large variety of cell surface receptors that are associated with acquisition of self-renewal and multipotent properties. Correct expression of these receptors depends on a delicate balance between cell surface trafficking, recycling, and degradation and is controlled by the microtubule network and Golgi apparatus, whose roles have hardly been explored during embryonic/fetal hematopoiesis. Here we show that, in the absence of CLASP2, a microtubule-associated protein, the overall production of HSCs is reduced, and the produced HSCs fail to self-renew and maintain their stemness throughout mouse and zebrafish development. This phenotype can be attributed to decreased cell surface expression of the hematopoietic receptor c-Kit, which originates from increased lysosomal degradation in combination with a reduction in trafficking to the plasma membrane. A dysfunctional Golgi apparatus in CLASP2-deficient HSCs seems to be the underlying cause of the c-Kit expression and signaling imbalance.

KW - Animals

KW - Hematopoiesis/genetics

KW - Hematopoietic Stem Cells/metabolism

KW - Mice

KW - Microtubule-Associated Proteins/metabolism

KW - Proto-Oncogene Proteins c-kit/metabolism

KW - Receptor Protein-Tyrosine Kinases/metabolism

KW - Zebrafish

U2 - 10.1016/j.celrep.2022.110957

DO - 10.1016/j.celrep.2022.110957

M3 - Article

C2 - 35705037

SN - 2211-1247

VL - 39

SP - 110957

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -