Jane Seymour is British. In fact, she used to be a Bond Girl. It's not exactly clear whether Quinn's accent is supposed to be some version of upper-class Bostonian; her family talks roughly the same way.
Cloud Dancing, a Cheyenne shaman, is played by Osage/Cherokee and Lakota actor Larry Sellers.
And several actors were swapped out after the pilot, including Colm Meaney as Jake Slicker.
Michaela's mother was originally played by Jane Wyman, who was later replaced by Georgann Johnson. Johnson stayed in the role for the remainder of the series.
Teresa was played by Michelle Bonilla in Season 5, Alex Meneses in Season 6
Promoted Fanboy: When Fred Rogers mentioned in an interview that Dr. Quinn was one of the few TV shows he enjoyed watching, the producers arranged for him to become a Guest Star. He played the role of "Reverend Thomas", his only on-camera appearance as a fictional human character.