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Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow

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Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow

dc.contributor.author	Zheng, Junke
dc.contributor.author	Lu, Zhigang
dc.contributor.author	Kocabas, Fatih
dc.contributor.author	Böttcher, Ralph T.
dc.contributor.author	Costell Rosselló, Mercedes
dc.contributor.author	Kang, Xunlei
dc.contributor.author	Liu, Xiaoye
dc.contributor.author	DeBerardinis, Ralph J.
dc.contributor.author	Wang, Qianming
dc.contributor.author	Chen, Guo-Qiang
dc.contributor.author	Sadek, Hesham
dc.contributor.author	Zhang, Cheng Cheng
dc.date.accessioned	2016-07-20T15:00:34Z
dc.date.available	2016-07-20T15:00:34Z
dc.date.issued	2014
dc.identifier.citation	Zheng, Junke Lu, Zhigang Kocabas, Fatih Böttcher, Ralph T. Costell Rosselló, Mercedes Kang, Xunlei Liu, Xiaoye DeBerardinis, Ralph J. Wang, Qianming Chen, Guo-Qiang Sadek, Hesham Zhang, Cheng Cheng 2014 Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow Blood 123 7 992 1001
dc.identifier.uri	http://hdl.handle.net/10550/54642
dc.description.abstract	How stem cells interact with the microenvironment to regulate their cell fates and metabolism is largely unknown. Here we demonstrated that the deletion of the cytoskeleton-modulating protein profilin 1 (pfn1) in hematopoietic stem cell (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. A switch from glycolysis to mitochondrial respiration with increased reactive oxygen species (ROS) level was also observed in HSCs on pfn1 deletion. Importantly, treatment of pfn1-deficient mice with the antioxidant N-acetyl-l-cysteine reversed the ROS level and loss of quiescence of HSCs, suggesting that the metabolism is mechanistically linked to the cell cycle quiescence of stem cells. The actin-binding and proline-binding activities of pfn1 are required for its function in HSCs. Our study provided evidence that pfn1 at least partially acts through the axis of pfn1/Gα13/EGR1 to regulate stem cell retention and metabolism in the bone marrow.
dc.language.iso	eng
dc.relation.ispartof	Blood, 2014, vol. 123, num. 7, p. 992-1001
dc.subject	Cèl·lules mare
dc.subject	Proteïnes
dc.title	Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow
dc.type	journal article	es_ES
dc.date.updated	2016-07-20T15:00:34Z
dc.identifier.doi	10.1182/blood-2013-04-498469
dc.identifier.idgrec	111996
dc.rights.accessRights	open access	es_ES