Unit
STEM CELL MOLECULAR GENETICS
Description
Stem cells can be found in many tissues where they are able to self-renew and differentiate into their progeny. Our lab is interested in identifying the role that TET3 plays on stem cell biology and whether a TET3 malfunction might lead to disease. To this end, we use the intestinal and testicular epithelia as models.
In the intestinal model, we study TET3 function on intestinal stem cell differentiation using mouse models in which Tet3 has been deleted. Although Tet3 knockout mice show perinatal lethality, the intestinal epithelium is totally developed at birth. Thus, we can still compare the Tet3 knockout intestinal epithelium to their wild-type counterpart and, then, infer Tet3 function. Furthermore, we use intestinal organoids to study the long-term effect of TET3 deletion. In our last study (Mulet et al., 2024 Nature Communications), we have demonstrated that Tet3 loss leads to enterocytes with an aberrant metabolic profile that might predispose them to tumorigenesis, a hypothesis that we are currently testing.
In contrast to the intestinal epithelium, newborn mice lack spermatogenesis and, to date, testicular organoids have not been described yet. Thus, we take advantage of spermatogonial stem cell lines to study the role of Tet3 in spermatogenesis. Indeed, we first delete Tet3 in spermatogonial stem cell lines that are subsequently transplanted into wild-type testes. Using this strategy, we can study in vivo the short- and long-term effects of TET3 loss on spermatogenesis. Furthermore, spermatogonial stem cells can spontaneously reprogram to a pluripotent state in a process that resembles the induction of testicular in situ carcinomas, thus providing a useful tool to study in vitro a putative contribution of TET3 on testicular oncogenesis.
Tet3 expression pattern in the intestinal epithelium.
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