2026-08-29T10:01:20Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/52512024-09-27T09:03:16Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Leiva, Magdalena
author
Quintana, Juan A.
author
Ligos, Jose M.
author
Hidalgo, Andres
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Fundación ProCNIC
2017-10-30T13:32:27Z
2017-10-30T13:32:27Z
2016
Nat Commun. 2016; 7:10222
10.1038/ncomms10222
2041-1723
Nature Communications
26742601
http://hdl.handle.net/20.500.12105/5251
The life-long maintenance of haematopoietic stem and progenitor cells (HSPCs) critically relies on environmental signals produced by cells that constitute the haematopoietic niche. Here we report a cell-intrinsic mechanism whereby haematopoietic cells limit proliferation within the bone marrow, and show that this pathway is repressed by E-selectin ligand 1 (ESL-1). Mice deficient in ESL-1 display aberrant HSPC quiescence, expansion of the immature pool and reduction in niche size. Remarkably, the traits were transplantable and dominant when mutant and wild-type precursors coexisted in the same environment, but were independent of E-selectin, the vascular receptor for ESL-1. Instead, quiescence is generated by unrestrained production of the cytokine TGF beta by mutant HSPC, and in vivo or in vitro blockade of the cytokine completely restores the homeostatic properties of the haematopoietic niche. These findings reveal that haematopoietic cells, including the more primitive compartment, can actively shape their own environment.
eng
E-SELECTIN LIGANDS
TRANSFORMING GROWTH-FACTOR-BETA-1
PROGENITOR CELLS
NICHE
QUIESCENCE
IDENTIFICATION
MACROPHAGES
NEUTROPHILS
HIBERNATION
TGF-BETA-1
Haematopoietic ESL-1 enables stem cell proliferation in the bone marrow by limiting TGF beta availability
journal article
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HaematopoieticESL-1EnablesStem_2016
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HaematopoieticESL-1EnablesStem_2016.txt