Roles of Heparan sulfate in mesendoderm differentiation of human embryonic stem cells

Thesis: S.M., Massachusetts Institute of Technology, Department of Chemistry, 2019

Bibliographic Details
Main Author: Li, Qiao,S. M.Massachusetts Institute of Technology.
Other Authors: Laura L. Kiessling.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2019
Subjects:
Online Access:https://hdl.handle.net/1721.1/121785
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author Li, Qiao,S. M.Massachusetts Institute of Technology.
author2 Laura L. Kiessling.
author_facet Laura L. Kiessling.
Li, Qiao,S. M.Massachusetts Institute of Technology.
author_sort Li, Qiao,S. M.Massachusetts Institute of Technology.
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description Thesis: S.M., Massachusetts Institute of Technology, Department of Chemistry, 2019
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spelling mit-1721.1/1217852019-09-13T03:06:07Z Roles of Heparan sulfate in mesendoderm differentiation of human embryonic stem cells Li, Qiao,S. M.Massachusetts Institute of Technology. Laura L. Kiessling. Massachusetts Institute of Technology. Department of Chemistry. Massachusetts Institute of Technology. Department of Chemistry Chemistry. Thesis: S.M., Massachusetts Institute of Technology, Department of Chemistry, 2019 Cataloged from PDF version of thesis. Includes bibliographical references (pages 61-68). Human embryonic stem cells (hESCs) are remarkable for their ability to self-renew indefinitely and differentiate into any cell type in the human body. The differentiation of hESCs is regulated by intrinsic and extrinsic signals in the stem cell niche. Heparan sulfate proteoglycans (HSPGs) are found on the membrane of all animal cells and have long been implicated in a wide range of cell-cell signaling and cell-matrix interactions. Multiple heparan sulfate (HS)-binding growth factors, such as Wnt, bone morphogenetic proteins (BMP), and fibroblast growth factor (FGF), critically regulate cell fate decisions of ES cells. Here, we showed that HS-deficient derived from hESCs have impaired ability to differentiate into Brachyury-positive mesendoderm (ME) cells. Exogenous addition of heparin partially rescued ME differentiation defect. Furthermore, examination of developmental signaling pathways revealed that HS ablation diminished FGF, Activin A and BMP signaling in differentiated cells. RNA-Seq revealed other biological processes affected by HS deficiency including neurogenesis, bone development and immune responses. Understanding the roles of HS in specific molecular mechanisms that regulate cell fates may provide insights into the complex molecular mechanisms underlying HS-associated human diseases and therefore facilitate the development of therapeutics. by Qiao Li. S.M. S.M. Massachusetts Institute of Technology, Department of Chemistry 2019-07-18T20:28:56Z 2019-07-18T20:28:56Z 2019 2019 Thesis https://hdl.handle.net/1721.1/121785 1103441214 eng MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/7582 68 pages application/pdf Massachusetts Institute of Technology
spellingShingle Chemistry.
Li, Qiao,S. M.Massachusetts Institute of Technology.
Roles of Heparan sulfate in mesendoderm differentiation of human embryonic stem cells
title Roles of Heparan sulfate in mesendoderm differentiation of human embryonic stem cells
title_full Roles of Heparan sulfate in mesendoderm differentiation of human embryonic stem cells
title_fullStr Roles of Heparan sulfate in mesendoderm differentiation of human embryonic stem cells
title_full_unstemmed Roles of Heparan sulfate in mesendoderm differentiation of human embryonic stem cells
title_short Roles of Heparan sulfate in mesendoderm differentiation of human embryonic stem cells
title_sort roles of heparan sulfate in mesendoderm differentiation of human embryonic stem cells
topic Chemistry.
url https://hdl.handle.net/1721.1/121785
work_keys_str_mv AT liqiaosmmassachusettsinstituteoftechnology rolesofheparansulfateinmesendodermdifferentiationofhumanembryonicstemcells