High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice
Blood formation by hematopoietic stem cells (HSCs) is regulated by a still incompletely defined network of general and HSC-specific regulators. In this study, we analyzed the role of G-protein coupled receptor 56 (Gpr56) as a candidate HSC regulator based on its differential expression in quiescent...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-05-01
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| Series: | Stem Cell Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506115000288 |
| _version_ | 1818906512446193664 |
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| author | Tata Nageswara Rao Jonathan Marks-Bluth Jessica Sullivan Manoj K. Gupta Vashe Chandrakanthan Simon R. Fitch Katrin Ottersbach Young C. Jang Xianhua Piao Rohit N. Kulkarni Thomas Serwold John E. Pimanda Amy J. Wagers |
| author_facet | Tata Nageswara Rao Jonathan Marks-Bluth Jessica Sullivan Manoj K. Gupta Vashe Chandrakanthan Simon R. Fitch Katrin Ottersbach Young C. Jang Xianhua Piao Rohit N. Kulkarni Thomas Serwold John E. Pimanda Amy J. Wagers |
| author_sort | Tata Nageswara Rao |
| collection | DOAJ |
| description | Blood formation by hematopoietic stem cells (HSCs) is regulated by a still incompletely defined network of general and HSC-specific regulators. In this study, we analyzed the role of G-protein coupled receptor 56 (Gpr56) as a candidate HSC regulator based on its differential expression in quiescent relative to proliferating HSCs and its common targeting by core HSC regulators. Detailed expression analysis revealed that Gpr56 is abundantly expressed by HSPCs during definitive hematopoiesis in the embryo and in the adult bone marrow, but its levels are reduced substantially as HSPCs differentiate. However, despite enriched expression in HSPCs, Gpr56-deficiency did not impair HSPC maintenance or function during steady-state or myeloablative stress-induced hematopoiesis. Gpr56-deficient HSCs also responded normally to physiological and pharmacological mobilization signals, despite the reported role of this GPCR as a regulator of cell adhesion and migration in neuronal cells. Moreover, Gpr56-deficient bone marrow engrafted with equivalent efficiency as wild-type HSCs in primary recipients; however, their reconstituting ability was reduced when subjected to serial transplantation. These data indicate that although GPR56 is abundantly and selectively expressed by primitive HSPCs, its high level expression is largely dispensable for steady-state and regenerative hematopoiesis. |
| first_indexed | 2024-12-19T21:40:24Z |
| format | Article |
| id | doaj.art-e179e95bfa164c25846232d5de988b07 |
| institution | Directory Open Access Journal |
| issn | 1873-5061 1876-7753 |
| language | English |
| last_indexed | 2024-12-19T21:40:24Z |
| publishDate | 2015-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-e179e95bfa164c25846232d5de988b072022-12-21T20:04:40ZengElsevierStem Cell Research1873-50611876-77532015-05-0114330732210.1016/j.scr.2015.02.001High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in miceTata Nageswara Rao0Jonathan Marks-Bluth1Jessica Sullivan2Manoj K. Gupta3Vashe Chandrakanthan4Simon R. Fitch5Katrin Ottersbach6Young C. Jang7Xianhua Piao8Rohit N. Kulkarni9Thomas Serwold10John E. Pimanda11Amy J. Wagers12Howard Hughes Medical Institute, USALowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, AustraliaHoward Hughes Medical Institute, USAJoslin Diabetes Center, Boston, MA 02215, USALowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, AustraliaDepartment of Haematology, Cambridge Institute for Medical Research University of Cambridge, Cambridge CB2 0XY, UKDepartment of Haematology, Cambridge Institute for Medical Research University of Cambridge, Cambridge CB2 0XY, UKHoward Hughes Medical Institute, USADivision of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, MA, USAJoslin Diabetes Center, Boston, MA 02215, USAJoslin Diabetes Center, Boston, MA 02215, USALowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, AustraliaHoward Hughes Medical Institute, USABlood formation by hematopoietic stem cells (HSCs) is regulated by a still incompletely defined network of general and HSC-specific regulators. In this study, we analyzed the role of G-protein coupled receptor 56 (Gpr56) as a candidate HSC regulator based on its differential expression in quiescent relative to proliferating HSCs and its common targeting by core HSC regulators. Detailed expression analysis revealed that Gpr56 is abundantly expressed by HSPCs during definitive hematopoiesis in the embryo and in the adult bone marrow, but its levels are reduced substantially as HSPCs differentiate. However, despite enriched expression in HSPCs, Gpr56-deficiency did not impair HSPC maintenance or function during steady-state or myeloablative stress-induced hematopoiesis. Gpr56-deficient HSCs also responded normally to physiological and pharmacological mobilization signals, despite the reported role of this GPCR as a regulator of cell adhesion and migration in neuronal cells. Moreover, Gpr56-deficient bone marrow engrafted with equivalent efficiency as wild-type HSCs in primary recipients; however, their reconstituting ability was reduced when subjected to serial transplantation. These data indicate that although GPR56 is abundantly and selectively expressed by primitive HSPCs, its high level expression is largely dispensable for steady-state and regenerative hematopoiesis.http://www.sciencedirect.com/science/article/pii/S1873506115000288 |
| spellingShingle | Tata Nageswara Rao Jonathan Marks-Bluth Jessica Sullivan Manoj K. Gupta Vashe Chandrakanthan Simon R. Fitch Katrin Ottersbach Young C. Jang Xianhua Piao Rohit N. Kulkarni Thomas Serwold John E. Pimanda Amy J. Wagers High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice Stem Cell Research |
| title | High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice |
| title_full | High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice |
| title_fullStr | High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice |
| title_full_unstemmed | High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice |
| title_short | High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice |
| title_sort | high level gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice |
| url | http://www.sciencedirect.com/science/article/pii/S1873506115000288 |
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