Abstract

Self renewal is one of the two defining properties of a stem cell, and understanding the mechanisms that govern self renewal is among the most important problems in stem cell biology. Unlike mouse, very little is known about the self renewal program of human embryonic stem cells (hESCs), which require undefined or extremely complex culture conditions. We have recently found a simple way to culture mouse, rhesus and human ES cells using a low concentration of butyrate which, in hESCs, activates an alternative and molecularly distinct transcriptional program. We hypothesize that the distinct transcriptional profile induced by butyrate is causally linked to, rather than reflective of, the butyrate self renewal program. This Project proposes to use butyrate and other recent developments from our lab to probe the molecular underpinnings of hESC self renewal.
In Specific Aim 1 we will distinguish whether butyrate selects for self renewing hESCs or reprograms hESCs In Specific Aim 2 we will examine whether butyrate's effects on hESCs are reversible.
In Specific Aim 3 we will identify butyrate responsive genes that are necessary or sufficient for hESC self renewal.
In Specific Aim 4 we will examine specific genomic loci that appear to be coordinately regulated by butyrate.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM081619-02
Application #
7664937
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
2
Fiscal Year
2008
Total Cost
$368,377
Indirect Cost

  Institution

Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Hofsteen, Peter; Robitaille, Aaron Mark; Strash, Nicholas et al. (2018) ALPK2 Promotes Cardiogenesis in Zebrafish and Human Pluripotent Stem Cells. iScience 2:88-100
Kim, Yong Kyun; Refaeli, Ido; Brooks, Craig R et al. (2017) Gene-Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development. Stem Cells 35:2366-2378
Artoni, Filippo; Kreipke, Rebecca E; Palmeira, Ondina et al. (2017) Loss of foxo rescues stem cell aging in Drosophila germ line. Elife 6:
Palpant, Nathan J; Pabon, Lil; Friedman, Clayton E et al. (2017) Generating high-purity cardiac and endothelial derivatives from patterned mesoderm using human pluripotent stem cells. Nat Protoc 12:15-31
Yang, Xiulan; Murry, Charles E (2017) One Stride Forward: Maturation and Scalable Production of Engineered Human Myocardium. Circulation 135:1848-1850
Kadota, Shin; Pabon, Lil; Reinecke, Hans et al. (2017) In Vivo Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Neonatal and Adult Rat Hearts. Stem Cell Reports 8:278-289
Nakamura, Paul A; Shimchuk, Andy A; Tang, Shibing et al. (2017) Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa. Elife 6:
Moody, James D; Levy, Shiri; Mathieu, Julie et al. (2017) First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor. Proc Natl Acad Sci U S A 114:10125-10130
Mathieu, Julie; Ruohola-Baker, Hannele (2017) Metabolic remodeling during the loss and acquisition of pluripotency. Development 144:541-551
Rabinowitz, Jeremy S; Robitaille, Aaron M; Wang, Yuliang et al. (2017) Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish. Proc Natl Acad Sci U S A 114:E717-E726

Showing the most recent 10 out of 114 publications