Human development and disease : lessons from induced pluripotent stem cells with X chromosome aneuploidies
Abstract/Contents
- Abstract
- 1 -- 2% of all human fetal conceptions result in Turner syndrome -- the complete or partial loss of the second sex chromosome (45, X karyotype). 90% of Turner cases terminate in spontaneous abortion during the first two trimesters; however, those who survive have a wide array of clinical characteristics. Infertility is very common in Turner syndrome women, making a link between the X chromosome and causes of infertility. Induced pluripotent stem cells (iPSCs) offer a means of obtaining insight on the genetic requirements of germ cell development. I have used iPSCs to characterize XIST, a non-coding RNA that initiates X chromosome inactivation (XCI), and shown that newly reprogrammed female iPSCs reflect the developmental state of the preimplanation embryo following embryonic genome activation. From the generation of iPSCs from four Turner syndrome, one premature ovarian failure and a control female, I demonstrated that two X chromosomes are not necessary for reprogramming to pluripotency. Single cell analysis of genes that escape XCI within control, Turner syndrome and Triple X iPSCs revealed minimal expression differences when compared to a female human embryonic stem cell (hESC) line. Next, I investigated the ability of X chromosome aneuploidy and control iPSCs to form germ cells by differentiating iPSCs and analyzing single cells and populations throughout a differentiation protocol using BMP4/8 and Retinoic acid. An increase in germ cell associated genes was not observed, but rather a loss. Finally, xenotransplantation was used to assess germ cell formation across different X chromosome aneuploidy states. All lines were capable of forming early germ cells in vivo, independent of their X chromosome composition. These results demonstrate that two complete X chromosomes are not necessary for the formation of early germ cells, and X aneuploidy iPSCs are amenable for the study for germ cell formation.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Dominguez, Antonia Alisia |
|---|---|
| Associated with | Stanford University, Department of Genetics. |
| Primary advisor | Reijo Pera, Renee |
| Thesis advisor | Reijo Pera, Renee |
| Thesis advisor | Baker, Julie, (Professor of genetics) |
| Thesis advisor | Brunet, Anne, 1972- |
| Thesis advisor | Snyder, Michael, Ph. D |
| Advisor | Baker, Julie, (Professor of genetics) |
| Advisor | Brunet, Anne, 1972- |
| Advisor | Snyder, Michael, Ph. D |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Antonia Alisia Dominguez. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Antonia Alisia Dominguez
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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