Evidence that Growth factor independence 1b regulates dormancy and peripheral blood mobilization of hematopoietic stem cells

Khandanpour, Cyrus; Sharif-Askari, Ehssan; Vaßen, Lothar; Gaudreau, Marie-Claude; Zhu, Jinfang; Paul, William E.; Okayama, Taro; Kosan, Christian; Möröy, Tarik

doi:10.1182/blood-2010-04-280305

Cited by 69 publications

(115 citation statements)

References 50 publications

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“…Detailed data regarding adult progenitor compartments in the Gfi1b loss-of-function context have not yet been published. Nevertheless, the severe thrombocytopenia and anemia of Gfi1b-null mice 40 reflect our findings in LSD1-kd mice. Also in concordance with our findings in adult LSD1-kd mice, analysis of the constitutive Gfi1b-null embryos revealed that Gfi1b is a key regulator of megakaryopoiesis and definitive erythropoiesis.…”

Section: Discussionsupporting

confidence: 87%

“…43 However, Gfi1-deficient HSCs displayed impaired self-renewal capacity in competitive repopulation assays whereas the self-renewal of Gfi1b-deficient HSCs remained unaltered. 40 Interestingly, conditional deletion of Gfi1b resulted in expanded phenotypic HSCs, which parallels our findings in LSD1-kd mice. We observed decreased G 0 and increased G 1 cell cycle fractions within LSD1-kd HSCs.…”

Section: Discussionsupporting

confidence: 87%

“…11 Gfi1b expression was also shown to be highest in HSCs and megakaryoerythroid progenitors in Gfi1b:GFP mice, and GFP expression directly correlated with Gfi1b expression. 22,40 We compared GFP expression in bone marrow progenitor cells from dox-treated shLSD1;Gfi1b:GFP and dox-treated littermate Gfi1b:GFP control mice. Strikingly, LSD1-kd abolished the dichotomy of GFP expression reported for Gfi1b-GFP c-kit þ Sca-1 À lin À progenitor cells 22 and resulted in an excessive GFP upregulation.…”

Section: Resultsmentioning

confidence: 99%

“…24 The quiescent G 0 HSC compartment of Gfi1b-deficient HSCs was not directly assayed, but in competitive repopulation assays, the multilineage-repopulation capacity of Gfi1b-deficent HSCs was comparable to controls. 40 This suggests that neither the loss of Gfi1b nor LSD1 function expands the dormant long-term repopulating HSC compartment. In contrast, we show HSC and progenitor compartments hierarchically downstream to be dramatically increased in LSD1-kd mice.…”

Section: Discussionmentioning

confidence: 99%

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Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation

Sprüssel¹,

Schulte²,

et al. 2012

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation

Sprüssel¹,

Schulte²,

et al. 2012

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“…GFI1B is a proto-oncogene and transcriptional regulator that with its paralog, GFI1, acts as a gene repressor during early hematopoietic stem cell development [22][23][24][25]. GFI1 primarily intervenes in myeloid and lymphoid generation and genetic variants cause neutropenia.…”

Section: Gfi1b Transcription Repressormentioning

confidence: 99%

Should any genetic defect affecting α‐granules in platelets be classified as gray platelet syndrome?

Nurden

2016

American J Hematol

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There is much current interest in the role of the platelet storage pool of α‐granule proteins both in hemostasis and non‐hemostatic events. As well as in the arrest of bleeding, the secreted proteins participate in wound healing, inflammation, and innate immunity while in pathology they may be actors in arterial thrombosis and atherosclerosis as well as cancer and metastasis. For a long time, gray platelet syndrome (GPS) has been regarded as the classic inherited platelet disorder caused by an absence of α‐granules and their contents. While NBEAL2 is the major source of mutations in GPS, other gene variants may give rise to significant α‐granule deficiencies in platelets. These include GATA1, VPS33B, or VIPAS39 in the arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome and now GFI1B. Nevertheless, many phenotypic differences are associated with mutations in these genes. This critical review was aimed to assess genotype/phenotype variability in disorders of platelet α‐granule biogenesis and to urge caution in grouping all genetic defects of α‐granules as GPS. Am. J. Hematol. 91:714–718, 2016. © 2016 Wiley Periodicals, Inc.

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Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture

et al. 2019

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Transcription factor (TF)‐based reprogramming of somatic tissues holds great promise for regenerative medicine. Previously, we demonstrated that the TFs GATA2, GFI1B, and FOS convert mouse and human fibroblasts to hemogenic endothelial‐like precursors that generate hematopoietic stem progenitor (HSPC)‐like cells over time. This conversion is lacking in robustness both in yield and biological function. Herein, we show that inclusion of GFI1 to the reprogramming cocktail significantly expands the HSPC‐like population. AFT024 coculture imparts functional potential to these cells and allows quantification of stem cell frequency. Altogether, we demonstrate an improved human hemogenic induction protocol that could provide a valuable human in vitro model of hematopoiesis for disease modeling and a platform for cell‐based therapeutics. Database Gene expression data are available in the Gene Expression Omnibus (GEO) database under the accession number http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130361.

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Evidence that Growth factor independence 1b regulates dormancy and peripheral blood mobilization of hematopoietic stem cells

Cited by 69 publications

References 50 publications

Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation

Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation

Should any genetic defect affecting α‐granules in platelets be classified as gray platelet syndrome?

Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture

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