Dataset: Transcription profiling of mouse gain- and loss-of-function Hedgehod (Hh) genetic models reveals Hedgehog signaling is dispensable for adult hematopoietic stem cell function

The Hedgehog (Hh) signaling pathway is a developmentally conserved regulator of stem cell function. Several reports suggested that Hh signaling is an important regulator of hematopoietic stem cell (HSC) maintenance and differentiation. Here we test this hypothesis in vivo using both gain- and loss-of-function Hh genetic models. Surprisingly, our studies demonstrate that conditional Smoothened (Smo) deletion or over-activation has no significant effects on adult HSC self-renewal and function. Moreover, they indicate a lack of synergism between the Notch and Hh pathways in HSC function, as RBPJ- and Smo-deficiency do not affect hematopoiesis. In agreement with this notion, detailed genome-wide transcriptome analysis reveals that silencing of Hh signaling does not significantly alter the HSC-specific gene expression “signature”. Our studies demonstrate that the Hh signaling pathway is dispensable for adult HSC function and suggest that the Hh pathway can be targeted in future clinical trials addressing the effect of Hh inhibition on leukemia-initiating cell maintenance. Transcriptional consequences of inactivating Smo (hh loss-of-function) in LKS cells. Experiment Overall Design: Four samples were analyzed: wild-type (WT) control and Smo-deficient (SMO) Lin-ckit+Sca1+ (LSK) cells, as well as Lin-ckit+Sca1- myeloid progenitor (MP) cells, which served as a control for LSK-enriched/specific genes. Total bone marrow cells were pooled from four WT and four SMO mice before sorting LSK and MP populations.

Species:

mouse

Samples:

4

Source:

E-GEOD-15194

Updated:

Dec.12, 2014

Registered:

Nov.11, 2014