{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:15:37Z","timestamp":1790745337660,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2016,3,28]],"date-time":"2016-03-28T00:00:00Z","timestamp":1459123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"R01","award":["R01CA152108"],"award-info":[{"award-number":["R01CA152108"]}]},{"name":"R01","award":["R01HL113066"],"award-info":[{"award-number":["R01HL113066"]}]},{"name":"NIH\/NCI","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Previous studies indicate that Kras is dispensable for fetal liver hematopoiesis, but its role in adult hematopoiesis remains unclear. Here, we generated a Kras conditional knockout allele to address this question. Deletion of Kras in adult bone marrow (BM) is mediated by Vav-Cre or inducible Mx1-Cre. We find that loss of Kras leads to greatly reduced thrombopoietin (TPO) signaling in hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), while stem cell factor-evoked ERK1\/2 activation is not affected. The compromised TPO signaling is associated with reduced long term- and intermediate-term HSC compartments and a bias toward myeloid differentiation in MPPs. Although granulocyte macrophage colony-stimulating factor (GM-CSF)-evoked ERK1\/2 activation is only moderately decreased in Kras-\/- myeloid progenitors, it is blunted in neutrophils and neutrophil survival is significantly reduced in vitro. At 9-12 months old, Kras conditional knockout mice develop profound hematopoietic defects, including splenomegaly, an expanded neutrophil compartment, and reduced B cell number. In a serial transplantation assay, the reconstitution potential of Kras-\/- BM cells is greatly compromised, which is attributable to defects in the self-renewal of Kras-\/- HSCs and defects in differentiated hematopoietic cells. Our results demonstrate that Kras is a major regulator of TPO and GM-CSF signaling in specific populations of hematopoietic cells and its function is required for adult hematopoiesis.<\/jats:p>","DOI":"10.1002\/stem.2355","type":"journal-article","created":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T06:34:40Z","timestamp":1457937280000},"page":"1859-1871","source":"Crossref","is-referenced-by-count":43,"title":["<i>Kras<\/i> is Required for Adult Hematopoiesis"],"prefix":"10.1093","volume":"34","author":[{"given":"Alisa","family":"Damnernsawad","sequence":"first","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyao","family":"Kong","sequence":"additional","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Wen","sequence":"additional","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangang","family":"Liu","sequence":"additional","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adhithi","family":"Rajagopalan","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology Program, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaona","family":"You","sequence":"additional","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyong","family":"Wang","sequence":"additional","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhou","sequence":"additional","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik A.","family":"Ranheim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo R.","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Harvard Medical School and Boston Children's Hospital, Boston Children's Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Department of Neurology, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,3,28]]},"reference":[{"key":"2022010817000048500_stem2355-bib-0001","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/ni1560","article-title":"Of lineage and legacy: The development of mammalian hematopoietic stem cells","volume":"9","author":"Dzierzak","year":"2008","journal-title":"Nat 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