Environmental Control of Spermatogonial Stem Cell States Reveals Functional and Signaling Heterogeneity
Adult tissue stem cells often exist as heterogeneous populations, yet whether this heterogeneity
reflects intrinsically distinct cell types or reversible states imposed by the environment remains
unclear. In this seminar, I will present our work using mouse spermatogonial stem cells (SSCs)
as a model to address this question. By combining in vivo-defined state signatures, single-cell
transcriptomics, transplantation assays, and reporter-based analyses, we found that SSC state
identity is not fixed, but can be selectively imposed and reversibly controlled by extracellular
cues in vitro. Defined culture conditions stabilized highly homogeneous opposing SSC states
with distinct molecular and functional properties, enabling direct comparison of stem cell
behaviors that are otherwise obscured in mixed populations. This experimental control further
revealed that signaling outputs are strongly state-dependent. In particular, AKT signaling
supported cellular output in one SSC state, but promoted state transition in another. These
findings provide an experimental framework for understanding how environment, cell state,
and stem cell function are linked in adult tissues.
