Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation

The bone marrow niche plays critical roles in hematopoietic recovery and hematopoietic stem cell (HSC) regeneration after myeloablative stress. However, it is not clear whether systemic factors beyond the local niche are required for these essential processes in vivo. Thrombopoietin (THPO) is a key...

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Autores principales:	Longfei Gao, Matthew Decker, Haidee Chen, Lei Ding
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	hematopoietic stem cell stress thrombopoietin myeloablation Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ff6541051e3a401e996d4e1ddb6f8866
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spelling	oai:doaj.org-article:ff6541051e3a401e996d4e1ddb6f88662021-11-30T10:05:45ZThrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation10.7554/eLife.698942050-084Xe69894https://doaj.org/article/ff6541051e3a401e996d4e1ddb6f88662021-08-01T00:00:00Zhttps://elifesciences.org/articles/69894https://doaj.org/toc/2050-084XThe bone marrow niche plays critical roles in hematopoietic recovery and hematopoietic stem cell (HSC) regeneration after myeloablative stress. However, it is not clear whether systemic factors beyond the local niche are required for these essential processes in vivo. Thrombopoietin (THPO) is a key cytokine promoting hematopoietic rebound after myeloablation and its transcripts are expressed by multiple cellular sources. The upregulation of bone marrow-derived THPO has been proposed to be crucial for hematopoietic recovery and HSC regeneration after stress. Nonetheless, the cellular source of THPO in myeloablative stress has never been investigated genetically. We assessed the functional sources of THPO following two common myeloablative perturbations: 5-fluorouracil (5-FU) administration and irradiation. Using a Thpo translational reporter, we found that the liver but not the bone marrow is the major source of THPO protein after myeloablation. Mice with conditional Thpo deletion from osteoblasts and/or bone marrow stromal cells showed normal recovery of HSCs and hematopoiesis after myeloablation. In contrast, mice with conditional Thpo deletion from hepatocytes showed significant defects in HSC regeneration and hematopoietic rebound after myeloablation. Thus, systemic THPO from the liver is necessary for HSC regeneration and hematopoietic recovery in myeloablative stress conditions.Longfei GaoMatthew DeckerHaidee ChenLei DingeLife Sciences Publications Ltdarticlehematopoietic stem cellstressthrombopoietinmyeloablationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hematopoietic stem cell stress thrombopoietin myeloablation Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	hematopoietic stem cell stress thrombopoietin myeloablation Medicine R Science Q Biology (General) QH301-705.5 Longfei Gao Matthew Decker Haidee Chen Lei Ding Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation
description	The bone marrow niche plays critical roles in hematopoietic recovery and hematopoietic stem cell (HSC) regeneration after myeloablative stress. However, it is not clear whether systemic factors beyond the local niche are required for these essential processes in vivo. Thrombopoietin (THPO) is a key cytokine promoting hematopoietic rebound after myeloablation and its transcripts are expressed by multiple cellular sources. The upregulation of bone marrow-derived THPO has been proposed to be crucial for hematopoietic recovery and HSC regeneration after stress. Nonetheless, the cellular source of THPO in myeloablative stress has never been investigated genetically. We assessed the functional sources of THPO following two common myeloablative perturbations: 5-fluorouracil (5-FU) administration and irradiation. Using a Thpo translational reporter, we found that the liver but not the bone marrow is the major source of THPO protein after myeloablation. Mice with conditional Thpo deletion from osteoblasts and/or bone marrow stromal cells showed normal recovery of HSCs and hematopoiesis after myeloablation. In contrast, mice with conditional Thpo deletion from hepatocytes showed significant defects in HSC regeneration and hematopoietic rebound after myeloablation. Thus, systemic THPO from the liver is necessary for HSC regeneration and hematopoietic recovery in myeloablative stress conditions.
format	article
author	Longfei Gao Matthew Decker Haidee Chen Lei Ding
author_facet	Longfei Gao Matthew Decker Haidee Chen Lei Ding
author_sort	Longfei Gao
title	Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation
title_short	Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation
title_full	Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation
title_fullStr	Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation
title_full_unstemmed	Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation
title_sort	thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/ff6541051e3a401e996d4e1ddb6f8866
work_keys_str_mv	AT longfeigao thrombopoietinfromhepatocytespromoteshematopoieticstemcellregenerationaftermyeloablation AT matthewdecker thrombopoietinfromhepatocytespromoteshematopoieticstemcellregenerationaftermyeloablation AT haideechen thrombopoietinfromhepatocytespromoteshematopoieticstemcellregenerationaftermyeloablation AT leiding thrombopoietinfromhepatocytespromoteshematopoieticstemcellregenerationaftermyeloablation
_version_	1718406723071377408

Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation

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