Tawny Newsome was a guest on the Greatest Trek podcast and talked about the parallel nature of having Jake Sisko in character talking to Sam the character, but also having it be a meta conversation of Cirroc Lofton the actor taking on a kind of mentorship role to Kerrice Brooks the actor, in the way that Avery Brooks was a mentor to him on DS9. This plot is why Sam was cast as a Black woman, to make the relationship between two Black characters be more meaningful to the audience, because the show isn’t just a story between two fictional space characters but also a dialogue and conversation with the Black fans watching it right now. The ‘sis’ thing was part of that.

If I were to extrapolate an in-universe reason, it’s because Sam is developing this bond with her idea of Sisko the Emissary and how he is becoming a father figure to her, as opposed to her overbearing actual-parents The Makers, that she mentally treats Jake Sisko as the brother she never had. And so her vision of Jake addresses her as ‘sis’. He does note that she’s the one in control of how this whole dialogue is playing out.