Derivation of New ICM-stage hESCs

Derivation of New ICM-stage hESCs

Funding Type: 
New Cell Lines
Grant Number: 
RL1-00642-B
Award Value: 
$778,859
Stem Cell Use: 
Embryonic Stem Cell
iPS Cell
Other
Cell Line Generation: 
Embryonic Stem Cell
iPS Cell
Other
Status: 
Closed
Public Abstract: 
Statement of Benefit to California: 
Progress Report: 

Year 1

During the reporting period, we have made significant progress toward the following research aims: (1) Established two screening assay conditions that allowed us to carry out high throughput screens of small molecules for enhancing conversion of conventional human ESCs to the earlier developmental naive state like murine embryonic stem cells. A couple of hit compounds were identified from the screen, and validated. (2). Established and characterized naive state human pluripotent cell lines converted from HUES7, HUES10 and classic H1. Human pluripotent stem cells in such naive state exhibit similar cellular behaviors, e.g., cell survival, proliferation, and responses to various signaling pathway modulations as mES cells. (3) Identified a new fundamental mechanism in such reprogramming/conversion process.

Year 2

During the reporting period, we have made significant progress toward discovering new molecules and conditions that can induce the generation of the earlier developmental, naïve state of pluripotency in human cells. Specifically, we have carried out additional high throughput screening of chemical libraries for enhancing conversion of conventional human embryonic stem cells to the earlier developmental, naive pluripotency state. Novel hit compounds were identified from the screen, and validated. To further improve and characterize the molecules, we established the synthetic chemistry to generate analogs of one compound series, have conducted structure-activity-relationship study, and found activity improved compounds. This also allowed generation of affinity chromatography probes for target identification. Furthermore, mechanistic studies suggested two distinct pathways that affect the conversion to naïve state.

© 2013 California Institute for Regenerative Medicine