Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation
An effect of thyroid hormone (TH) on erythropoiesis has been known for more than a century but the molecular mechanism(s) by which TH affects red cell formation is still elusive. Here we demonstrate an essential role of TH during terminal human erythroid cell differentiation; specific depletion of T...
| Main Authors: | , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Published: |
National Academy of Sciences (U.S.)
2018
|
| Online Access: | http://hdl.handle.net/1721.1/114926 https://orcid.org/0000-0002-7029-7415 |
| _version_ | 1826212948379435008 |
|---|---|
| author | Gao, Xiaofei Lee, Hsiang-Ying Li, Wenbo Barrasa, M. Inmaculada Ma, Qi Elmes, Russell R. Rosenfeld, Michael G. Platt, Randall Jeffrey Lodish, Harvey F |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Gao, Xiaofei Lee, Hsiang-Ying Li, Wenbo Barrasa, M. Inmaculada Ma, Qi Elmes, Russell R. Rosenfeld, Michael G. Platt, Randall Jeffrey Lodish, Harvey F |
| author_sort | Gao, Xiaofei |
| collection | MIT |
| description | An effect of thyroid hormone (TH) on erythropoiesis has been known for more than a century but the molecular mechanism(s) by which TH affects red cell formation is still elusive. Here we demonstrate an essential role of TH during terminal human erythroid cell differentiation; specific depletion of TH from the culture medium completely blocked terminal erythroid differentiation and enucleation. Treatment with TRβ agonists stimulated premature erythroblast differentiation in vivo and alleviated anemic symptoms in a chronic anemia mouse model by regulating erythroid gene expression. To identify factors that cooperate with TRβ during human erythroid terminal differentiation, we conducted RNA-seq in human reticulocytes and identified nuclear receptor coactivator 4 (NCOA4) as a critical regulator of terminal differentiation. Furthermore, Ncoa4 −/− mice are anemic in perinatal periods and fail to respond to TH by enhanced erythropoiesis. Genome-wide analysis suggests that TH promotes NCOA4 recruitment to chromatin regions that are in proximity to Pol II and are highly associated with transcripts abundant during terminal differentiation. Collectively, our results reveal the molecular mechanism by which TH functions during red blood cell formation, results that are potentially useful to treat certain anemias. Keywords: thyroid hormone; erythropoiesis; NCOA4; nuclear receptor |
| first_indexed | 2024-09-23T15:40:41Z |
| format | Article |
| id | mit-1721.1/114926 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:40:41Z |
| publishDate | 2018 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1149262022-09-29T15:28:11Z Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation Gao, Xiaofei Lee, Hsiang-Ying Li, Wenbo Barrasa, M. Inmaculada Ma, Qi Elmes, Russell R. Rosenfeld, Michael G. Platt, Randall Jeffrey Lodish, Harvey F Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Platt, Randall Jeffrey Lodish, Harvey F An effect of thyroid hormone (TH) on erythropoiesis has been known for more than a century but the molecular mechanism(s) by which TH affects red cell formation is still elusive. Here we demonstrate an essential role of TH during terminal human erythroid cell differentiation; specific depletion of TH from the culture medium completely blocked terminal erythroid differentiation and enucleation. Treatment with TRβ agonists stimulated premature erythroblast differentiation in vivo and alleviated anemic symptoms in a chronic anemia mouse model by regulating erythroid gene expression. To identify factors that cooperate with TRβ during human erythroid terminal differentiation, we conducted RNA-seq in human reticulocytes and identified nuclear receptor coactivator 4 (NCOA4) as a critical regulator of terminal differentiation. Furthermore, Ncoa4 −/− mice are anemic in perinatal periods and fail to respond to TH by enhanced erythropoiesis. Genome-wide analysis suggests that TH promotes NCOA4 recruitment to chromatin regions that are in proximity to Pol II and are highly associated with transcripts abundant during terminal differentiation. Collectively, our results reveal the molecular mechanism by which TH functions during red blood cell formation, results that are potentially useful to treat certain anemias. Keywords: thyroid hormone; erythropoiesis; NCOA4; nuclear receptor United States. Defense Advanced Research Projects Agency (Award HR0011-14-2-0005) United States. Department of Defense (Award W81WH-12-1-0449) National Heart, Lung, and Blood Institute (Grant P01 HL032262-25) 2018-04-24T14:51:25Z 2018-04-24T14:51:25Z 2017-09 2017-06 2018-04-20T16:13:40Z Article http://purl.org/eprint/type/ConferencePaper 0027-8424 1091-6490 http://hdl.handle.net/1721.1/114926 Gao, Xiaofei, et al. “Thyroid Hormone Receptor Beta and NCOA4 Regulate Terminal Erythrocyte Differentiation.” Proceedings of the National Academy of Sciences 114, 38 (September 2017): 10107–10112 © 2017 National Academy of Sciences https://orcid.org/0000-0002-7029-7415 http://dx.doi.org/10.1073/PNAS.1711058114 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences |
| spellingShingle | Gao, Xiaofei Lee, Hsiang-Ying Li, Wenbo Barrasa, M. Inmaculada Ma, Qi Elmes, Russell R. Rosenfeld, Michael G. Platt, Randall Jeffrey Lodish, Harvey F Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation |
| title | Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation |
| title_full | Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation |
| title_fullStr | Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation |
| title_full_unstemmed | Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation |
| title_short | Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation |
| title_sort | thyroid hormone receptor beta and ncoa4 regulate terminal erythrocyte differentiation |
| url | http://hdl.handle.net/1721.1/114926 https://orcid.org/0000-0002-7029-7415 |
| work_keys_str_mv | AT gaoxiaofei thyroidhormonereceptorbetaandncoa4regulateterminalerythrocytedifferentiation AT leehsiangying thyroidhormonereceptorbetaandncoa4regulateterminalerythrocytedifferentiation AT liwenbo thyroidhormonereceptorbetaandncoa4regulateterminalerythrocytedifferentiation AT barrasaminmaculada thyroidhormonereceptorbetaandncoa4regulateterminalerythrocytedifferentiation AT maqi thyroidhormonereceptorbetaandncoa4regulateterminalerythrocytedifferentiation AT elmesrussellr thyroidhormonereceptorbetaandncoa4regulateterminalerythrocytedifferentiation AT rosenfeldmichaelg thyroidhormonereceptorbetaandncoa4regulateterminalerythrocytedifferentiation AT plattrandalljeffrey thyroidhormonereceptorbetaandncoa4regulateterminalerythrocytedifferentiation AT lodishharveyf thyroidhormonereceptorbetaandncoa4regulateterminalerythrocytedifferentiation |