In the original, it was over Isaac’s mother bankrupting the family by selling all their assets to the Church.
The remake also changes the context of Isaac’s resentment towards Unitology. The remake also compounds this by revealing him and Nicole were near to having a falling out before the incident after Isaac's mother killed herself and Isaac's father due to a crisis of faith after Nicole tried to help her leave Unitology and Isaac, in misplaced anger, blamed her for it, which implies a greater sense of guilt from Isaac towards how he felt towards pushing for Nicole to go onto the Ishimura assignment in the later games. Owed to the fact he can now talk, the first game's remake has him vocally distraught at each of his Kellion crewmates dying, even Kendra note it helps that Kendra's undergone Adaptational Heroism, adding a layer of tragedy to her death. In Dead Space 3, he travels across the galaxy in hopes of stopping the Necromorph threat permanently. Unfortunately, another Necromorph attack happens there and Isaac has to once again fight to survive. By the time of Dead Space 2, his sanity has taken a couple of hits and he has been locked away in an asylum on Titan Station. 
He quickly finds that the Ishimura has been overrun with Necromorphs and has to fight through all of them while repairing the ship and rescuing Nicole. He is also looking for his girlfriend Nicole who is stationed there.
The star of the series, Isaac Clarke is an engineer with the CEC, dispatched on the USG Kellion to repair the Ishimura.
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