Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated membrane Beta1/Beta2-integrin expression


ABSTRACT: The Kruppel-like factor 5 (Klf5) regulates pluripotent stem cell self-renewal but its role in somatic stem cells is unknown. Klf5 deficient hematopoietic stem cells and progenitors (HSC/P) fail to engraft after transplantation. This HSC/P defect was associated with impaired bone marrow (BM) homing and lodging and decreased retention in BM. The Klf5Δ/Δ HSC/P homing defect associated with decreased adhesion to fibronectin and expression of membrane-bound β1/β2-integrins. In vivo inducible gain-of-function of Klf5 in HSC translated into increased HSC/P adhesion. The expression of Rab5 family members, mediators of β1/β2-integrin recycling in the early endosome, was decreased in Klf5Δ/Δ HSC/P. Klf5 binds directly to the promoter of Rab5a/b and overexpression of Rab5b rescued the expression of activated β1/β2-integrins, adhesion and BM homing of Klf5Δ/Δ HSC/P. Altogether, these data indicate that Klf5 is indispensable for adhesion, homing, lodging and retention of HSC/P in the BM through Rab5-dependent post-translational regulation of Beta1/Beta2 integrins. Differential gene expression analyses was performed with Affymetrix GeneChip Mouse 1.0 ST assay. LSK cells from KLF-/- (n=4) and wt (n=5), bred on a C57BL/6 background, was analyzed for differential gene expression using GeneSpring GX11 using student's T-test.

ORGANISM(S): Mus musculus

SUBMITTER: Jose Cancelas 

PROVIDER: E-GEOD-43806 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

altmetric image

Publications

Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated β1/β2-integrin trafficking.

Taniguchi Ishikawa E E   Chang K H KH   Nayak R R   Olsson H A HA   Ficker A M AM   Dunn S K SK   Madhu M N MN   Sengupta A A   Whitsett J A JA   Grimes H L HL   Cancelas J A JA  

Nature communications 20130101


Krüppel-like factor 5 regulates pluripotent stem cell self-renewal, but its role in somatic stem cells is unknown. Here we show that Krüppel-like factor 5-deficient haematopoietic stem cells and progenitors fail to engraft after transplantation. This haematopoietic stem cell and progenitor defect is associated with impaired bone marrow homing and lodging and decreased retention in bone marrow, and with decreased adhesion to fibronectin and expression of membrane-bound β1/β2-integrins. In vivo-in  ...[more]

Similar Datasets

2013-01-30 | GSE43806 | GEO
2020-07-20 | PXD017088 | Pride
| PRJNA187982 | ENA
2019-11-12 | PXD011134 | Pride
2019-11-12 | PXD011135 | Pride
2015-07-10 | E-GEOD-43806 | ExpressionAtlas
2022-06-17 | GSE206183 | GEO
2022-12-22 | PXD024000 | Pride
2023-10-24 | PXD037907 | Pride
2019-01-27 | GSE104908 | GEO