In this issue of Blood, Kabiri and coworkers report the hematopoietic deletion of the endoplasmic reticulum-localized O-acyltransferase porcupine (PORCN), which is necessary for acylation of Wnts in the endoplasmic reticulum, enabling their secretion and binding to the frizzled receptors. 1 Unexpectedly, the absence of secreted Wnt factors does not have major effects on steady-state in vivo hematopoiesis or on long-term repopulating activity of Wnt-deficient hematopoietic stem cells.
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