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Haematologica. 2019 Apr 19. pii: haematol.2018.207100. doi: 10.3324/haematol.2018.207100. [Epub ahead of print]

Ttc7a regulates haematopoietic stem cell functions while controlling the stress-induced response.

Author information

1
Imagine Institute. Université Paris Descartes -Sorbonne Paris Cité, France.
2
Bioinformatic Platform, Université Paris Descartes-Sorbonne Paris Cité, Paris.
3
Collège de France, Paris, France.
4
Laboratory of Normal and Pathological Homeostasis of the Immune System, Paris, France fernando.sepulveda@inserm.fr.

Abstract

The molecular machinery that regulates the balance between self-renewal and differentiation properties of hematopoietic stem cells has yet to be characterized in detail. Here we found that the tetratricopeptide repeat domain 7 A (Ttc7a) protein, a putative scaffold protein expressed by hematopoietic stem cells, acts as an intrinsic regulator of the proliferative response and the self- renewal potential of murine hematopoietic stem cells in vivo. Loss of Ttc7a consistently enhanced the hematopoietic stem cells' competitive repopulation ability and their intrinsic capacity to replenish the hematopoietic system after serial cell transplantations, relative to wild-type cells. Ttc7a-deficient hematopoietic stem cells exhibit a different transcriptomic profile for a set of genes controlling the cellular response to stress, which was associated with increased proliferation in response to chemically induced stress in vitro and myeloablative stress in vivo. Our results therefore revealed a previously unrecognized role of Ttc7a as a critical regulator of the hematopoietic stem cells stemness. This role is related, at least in part, to regulation of the endoplasmic reticulum stress response.

KEYWORDS:

ER stress; Hematopoiesis; Hematopoietic Stem Cell; Immunodeficiencies; TTC7A

PMID:
31004027
DOI:
10.3324/haematol.2018.207100
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