Preheat oven to 425 degrees F. Cut the butternut squash into 1-inch pieces. To a microwave-safe medium dish, add butternut squash and 3 tablespoons water. Season with salt and pepper. Cover with vented plastic and microwave 8-10 minutes, until tender. Drain and cool slightly.
To a blender or food processor, add half of the cooked butternut squash, cottage cheese, milk, mustard and hot sauce. Season well with salt and pepper. Puree until smooth.
Coat the inside of a 9x13-inch baking dish with the cooking spray. To a large bowl, add squash puree, butternut squash pieces, 1 1/2 cups Cheddar cheese and American cheese. Stir in the uncooked pasta. Transfer pasta mixture to baking dish and cover tightly with foil. Bake for 30 minutes.
Meanwhile, in a small bowl, combine remaining 1/2 cup grated Cheddar with bread crumbs, Parmesan, oil and thyme. Uncover the mac and cheese after 30 minutes and top with bread crumb mixture. Continue to bake 30 minutes more, until pasta is fully cooked and mixture is bubbly. Let mac and cheese rest for 10 minutes before serving.