scholarly journals Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation

2021 ◽  
Author(s):  
Lei Ding ◽  
Longfei Gao ◽  
Matthew Decker ◽  
Haidee Chen
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Critical Role ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery ◽  
Cellular Source ◽  
Systemic Factors

The bone marrow niche plays a critical role in hematopoietic recovery and hematopoietic stem cell (HSC) regeneration after myeloablation. However, it is not clear whether systemic factors beyond the local niche are required for these essential processes in vivo. Thrombopoietin (TPO) is a critical cytokine promoting hematopoietic rebound after myeloablation and its transcripts are expressed by multiple cellular sources. The upregulation of bone marrow-derived TPO has been proposed to be crucial for hematopoietic recovery and HSC regeneration after stress. Nonetheless, the cellular source of TPO in stress has never been investigated genetically. We assessed the functional sources of TPO following two common myeloablative perturbations: 5-fluorouracil (5-FU) administration and irradiation. Using a Tpo translational reporter, we found that the liver but not the bone marrow is the major source of TPO protein after myeloablation. Mice with conditional Tpo deletion from osteoblasts or bone marrow stromal cells showed normal recovery of HSCs and hematopoiesis after myeloablation. In contrast, mice with conditional Tpo deletion from hepatocytes showed significant defects in HSC regeneration and hematopoietic rebound after myeloablation. Thus, systemic TPO from the liver is necessary for HSC regeneration and hematopoietic recovery in myeloablative stress conditions.

scholarly journals Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Longfei Gao ◽  
Matthew Decker ◽  
Haidee Chen ◽  
Lei Ding
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Critical Role ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery ◽  
Cellular Source ◽  
Systemic Factors

The bone marrow niche plays a critical role 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 critical 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.

scholarly journals Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance

Science ◽  
2018 ◽  
Vol 360 (6384) ◽  
pp. 106-110 ◽  
Author(s):  
Matthew Decker ◽  
Juliana Leslie ◽  
Qingxue Liu ◽  
Lei Ding
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Bone Marrow Cells ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Stem Cell Maintenance ◽  
Extrinsic Cues ◽  
Systemic Factors ◽  
Made In

Hematopoietic stem cell (HSC) maintenance depends on extrinsic cues. Currently, only local signals arising from the bone marrow niche have been shown to maintain HSCs. However, it is not known whether systemic factors also sustain HSCs. We assessed the physiological source of thrombopoietin (TPO), a key cytokine required for maintaining HSCs. UsingTpoDsRed-CreERknock-in mice, we showed that TPO is expressed by hepatocytes but not by bone marrow cells. Deletion ofTpofrom hematopoietic cells, osteoblasts, or bone marrow mesenchymal stromal cells does not affect HSC number or function. However, whenTpois deleted from hepatocytes, bone marrow HSCs are depleted. Thus, a cross-organ factor, circulating TPO made in the liver by hepatocytes, is required for bone marrow HSC maintenance. Our results demonstrate that systemic factors, in addition to the local niche, are a critical extrinsic component for HSC maintenance.

PROSTACYCLIN IS A NOVEL HEMATOPOIETIC STEM CELL REGULATOR ENRICHED IN THE ENDOSTEAL BONE MARROW NICHE

2019 ◽  
Vol 76 ◽  
pp. S88
Author(s):  
Joshua Tay ◽  
Jean-Pierre Levesque ◽  
Falak Helwani ◽  
Gareth Price ◽  
Valerie Barbier ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem

Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2340-2342 ◽  
Author(s):  
Stéphane J. C. Mancini ◽  
Ned Mantei ◽  
Alexis Dumortier ◽  
Ueli Suter ◽  
H. Robson MacDonald ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Notch Signaling ◽  
Hematopoietic Stem Cell ◽  
Stromal Cells ◽  
Essential Role ◽  
Self Renewal ◽  
Hematopoietic Stem

AbstractJagged1-mediated Notch signaling has been suggested to be critically involved in hematopoietic stem cell (HSC) self-renewal. Unexpectedly, we report here that inducible Cre-loxP–mediated inactivation of the Jagged1 gene in bone marrow progenitors and/or bone marrow (BM) stromal cells does not impair HSC self-renewal or differentiation in all blood lineages. Mice with simultaneous inactivation of Jagged1 and Notch1 in the BM compartment survived normally following a 5FU-based in vivo challenge. In addition, Notch1-deficient HSCs were able to reconstitute mice with inactivated Jagged1 in the BM stroma even under competitive conditions. In contrast to earlier reports, these data exclude an essential role for Jagged1-mediated Notch signaling during hematopoiesis.

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