Data from: Role of mechanometabolism in hematopoietic stem cell specification

The mechanical force generated by blood flow stimulates emergence of the
first hematopoietic stem cells (HSCs) in the embryo that are critical for
producing the adult blood system. Fluid force drives transition of HSC
precursors from an endothelial to hematopoietic identity. Here, we provide
the source data for our study exploring the molecular regulation of this
fate switch. We identify a role for shear stress in driving the adaptation
of mitochondrial composition, ultrastructure, and function, which we show
are essential for hematopoietic fate specification and engraftment
potential. Data in support of characterization of Ncx1 cardiac mutants and
ex vivo shear stress cultures are supplied for all graphs in our study.
Briefly, we show that shear stress remodels mitochondria by promoting
mitochondrial gene transcription and protein synthesis. Laminar fluid flow
selectively initiates translation of 5’terminal polypyrimidine (5’TOP)
motif-containing transcripts, which commonly encode ribosome and
translation machinery. The metabolic reprogramming induced by flow depends
upon mTOR activation and is blocked when ribosome activity or mTOR is
inhibited. Conversely, chemical activation of mTOR mimics the effects of
fluid shear stress on mitochondria and blood reconstituting potential.
Further, we demonstrate that pharmacological activation of mTOR can also
partially rescue hematopoiesis in heartbeat mutants in utero. These data
reveal that mechanometabolism is a physiologically relevant determinant of
hematopoietic fate that could be leveraged for improved engineering of
HSCs for disease modeling and treatment.