1. Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC and/or IRB approval may still be required) Do I need to submit an hSCRO protocol or modification? Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes No Yes No Yes Do you intend to use an existing hiPSC line in your lab for the first time?

2. Some Specific Examples:

3. Please submit an hSCRO Protocol or modify an existing protocol Example 1: I want to work with iPSC-derived neural stem cells in vitro that I will purchase or receive from a collaborator (follow the green) Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes No Yes No Yes Do you intend to use an existing hiPSC line in your lab for the first time? Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC and/or IRB approval may still be required)

4. Please submit an hSCRO Protocol or modify an existing protocol Example 2: I want to make hiPSCs from human fibroblasts. (follow the green) Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes Do you intend to use an existing hiPSC line for the first time? No Yes No Yes Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC and/or IRB approval may still be required)

5. Please submit an hSCRO Protocol or modify an existing protocol Example 3: I want to study fetal-derived astrocytes. (follow the green) Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes No Yes No Yes Do you intend to use an existing hiPSC line in your lab for the first time? Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC and/or IRB approval may still be required)

6. Example 4: I want to purchase & use hiPSC-derived Hematopoietic Stem Cells (follow the green) Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes No Yes No Yes Do you intend to use an existing hiPSC line in your lab for the first time? Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC and/or IRB approval may still be required)

7. Please submit an hSCRO Protocol or modify an existing protocol Example 5: I want to use existing hiPSCs to generate & study neurons. (follow the green) Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes No Yes No Yes Do you intend to use an existing hiPSC line in your lab for the first time? Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC and/or IRB approval may still be required)

8. Example 6: I want to get hiPSC-derived neural stem cells from a collaborator and study them in vitro. (follow the green) Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes Do you intend to use an existing hiPSC line in your lab for the first time? No Yes No Yes Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC and/or IRB approval may still be required)

9. Please submit an hSCRO Protocol or modify an existing protocol Example 6: I want to use adult-derived mesenchymal stem cells. (follow the green) Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes No Yes No Yes Do you intend to use an existing hiPSC line in your lab for the first time? Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC and/or IRB approval may still be required)

10. Please submit an hSCRO Protocol or modify an existing protocol Example 6: I want to get adult autopsy-derived neural stem cells from a collaborator and study them in vivo. (follow the green) Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes No Yes No Yes Do you intend to use an existing hiPSC line in your lab for the first time? Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IACUC, IBC, and/or IRB approval may still be required)

11. Please submit an hSCRO Protocol or modify an existing protocol Example 7: I want to get adult autopsy-derived human microglia from a collaborator and transplant them into mice. (follow the green) Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IACUC, IBC, and IRB approval may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes No Yes No Yes Do you intend to use an existing hiPSC line in your lab for the first time? Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC and/or IRB approval may still be required)

12. Some examples that likely need additional discussion by the Working Group

13. Please submit an hSCRO Protocol or modify an existing protocol I would like to generate iPSCs from tissue obtained from the coroner’s office? Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes No Yes No Yes With this current flowchart this should lead to hSCRO review, but no consent or provenance documents are available for these samples. Should this type of research not be permitted? Do you intend to use an existing hiPSC line in your lab for the first time? Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC and/or IRB approval may still be required)

14. Please submit an hSCRO Protocol or modify an existing protocol I would like to generate iPSCs from subjects who have donated their brain in association with a UCI-approved IRB. Do you intend to use existing pluripotent human embryonic cells (hESCs) or generate new hESCs? (pluripotent=can differentiate into all 3 germ lineages) An hSCRO Protocol is Not required. However, IBC approval and/or an IRB Exemption may still be needed Do you plan on using cells Derived from human Fetal material? Yes Are the cells multipotent? (can give rise to Two or more cell types) No Yes No Are the cells multipotent Neural Stem Cells? No Yes Do you intend to Transplant them into an animal? No Do you intend to generate new human Induced pluripotent Stem cells (hiPSCs) lines? (pluripotent=can differentiate into all 3 germ lineages) No Yes No Yes No Yes What language would need to be Included in the brain donation IRB to allow iPSC generation from deceased individuals? Would that IRB consent need to specifically mention the potential for making stem cells, iPSCs, or would a broad consent suffice? Do you intend to use an existing hiPSC line in your lab for the first time? Please submit an hSCRO Protocol or modify an existing protocol. (Refer to Provenance policy document, IBC And/or IRB approval may still be required)