2026-04-29T23:04:22Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/83452024-10-31T11:42:56Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
advisor
Mercader, Nadia
author
Sanchez-Iranzo, Hector
funder
Ministerio de Educación y Ciencia (España)
funder
Unión Europea. Comisión Europea
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2019-09-13T13:03:30Z
2019-09-13T13:03:30Z
2017-01-09
10.4321/repisalud.8345
http://hdl.handle.net/20.500.12105/8345
The zebrafish is an established model organism to study heart regeneration, in which pre-existing cardiomyocytes (CMs) proliferate to replace the lost myocardium. During development, mesodermal progenitors from the first heart field (FHF) form a primitive cardiac tube, to which cells from the second heart field (SHF) are added. Here we investigated whether FHF and SHF derivatives in the zebrafish give rise to distinct CM populations, and examined the degree of cell fate plasticity of SHF derivatives during heart regeneration. Using tbx5a-lineage tracing we found that the adult zebrafish heart is also composed of CM populations from the FHF and SHF. Furthermore, ablation of FHF-derived CMs in the embryo is compensated by expansion of SHF derived cells. tbx5a lineage-tracing was also employed to investigate the fate of trabecular CMs during adult heart regeneration. While previous clonal analysis suggested that the different
myocardial layers are rebuilt by CMs within each layers, we describe that trabecular CMs can switch their fate and differentiate into cortical myocardium. Heart regeneration is preceded by a fibrotic response. Thus, fibrosis and regeneration are not mutually exclusive responses. Upon cardiac cryoinjury, collagen and other extracellular matrix (ECM) components accumulate at the injury site. Unlike the situation in mammals, fibrosis in zebrafish is transient and its regression is concomitant with regrowth of the myocardial wall. We describe that during fibrosis regression, fibroblasts are not fully eliminated and become inactivated. Unexpectedly, limiting the fibrotic response by genetic ablation of col1a2-expressing cells not only failed to enhance regeneration but also impaired CMs proliferation. We conclude that zebrafish regeneration is a process that
requires CM plasticity, and involves ECM-producing cells that become inactive and promote CMs proliferation.
eng
Zebrafish
Heart regeneration
Cardiomyocite
Plasticity
Fibroblast
Characterisation of cardiomyocyte plasticity and the role of fibroblast during zebrafish heart regeneration
doctoral thesis
TElDRU5DSUEgREUgRElTVFJJQlVDScOTTiBOTyBFWENMVVNJVkEKCkFjZXB0YW5kbyBlc3RhIGxpY2VuY2lhLCBVc3RlZCAoZWwgYXV0b3IvZXMgbyBlbCBwcm9waWV0YXJpby9zIGRlIGxvcyBkZXJlY2hvcyBkZSAKYXV0b3IpIGNvbmNlZGUgYSBSRVBJU0FMVUQgZWwgZGVyZWNobyBubyBleGNsdXNpdm8gZGUgcmVwcm9kdWNpciwgY29udmVydGlyLCB5L28gCmRpc3RyaWJ1aXIgc3UgZG9jdW1lbnRvIChpbmNsdXllbmRvIHN1IHJlc3VtZW4pIGEgbml2ZWwgbXVuZGlhbCBlbiBmb3JtYXRvIGRpZ2l0YWwsIAppbmNsdXllbmRvLCBhdWRpbyB5IHbDrWRlbywgYSB0cmF2w6lzIGRlIHN1IHJlcG9zaXRvcmlvIGluc3RpdHVjaW9uYWwuCgpVc3RlZCBhY2VwdGEgcXVlIFJFUElTQUxVRCBwdWVkZSwgc2luIGFsdGVyYXIgc3UgY29udGVuaWRvLCBjb252ZXJ0aXIgc3UgZG9jdW1lbnRvIAphIGN1YWxxdWllciBvdHJvIGZvcm1hdG8gZGlnaXRhbCBkZSBkYXRvcywgYXVkaW8geSB2aWRlbywgY29uIGVsIHByb3DDs3NpdG8gZGUgcXVlIApwdWVkYSBzZXIgYWxvamFkbyBlbiBlbCByZXBvc2l0b3Jpby4gCgpVc3RlZCBlc3TDoSBkZSBhY3VlcmRvIGNvbiBxdWUgUkVQSVNBTFVEIHB1ZWRhIGNvbnNlcnZhciBtw6FzIGRlIHVuYSBjb3BpYSBkZSBlc3RlIApkb2N1bWVudG8gcGFyYSBhc2VndXJhciBzdSBzZWd1cmlkYWQsIHByZXNlcnZhY2nDs24geSBhY2Nlc28uCgpVc3RlZCBkZWNsYXJhIHF1ZSBlbCBkb2N1bWVudG8gZXMgdW4gdHJhYmFqbyBvcmlnaW5hbCwgeSBxdWUgdGllbmUgZWwgZGVyZWNobyBkZSAKb3RvcmdhciBsb3MgZGVyZWNob3MgY29udGVuaWRvcyBlbiBlc3RhIGxpY2VuY2lhLiBUYW1iacOpbiBkZWNsYXJhIHF1ZSBzdSBwZXRpY2nDs24gCm5vIGluZnJpbmdlIGxvcyBkZXJlY2hvcyBkZSBhdXRvciBkZSBuYWRpZS4gCgpTaSBlbCBkb2N1bWVudG8gY29udGllbmUgbWF0ZXJpYWxlcyBwYXJhIGxvcyBxdWUgbm8gc2UgdGllbmVuIGxvcyBkZXJlY2hvcyBkZSBhdXRvciwgClVzdGVkIGRlY2xhcmEgcXVlIGhhIG9idGVuaWRvIGVsIHBlcm1pc28gc2luIHJlc3RyaWNjacOzbiBkZWwgcHJvcGlldGFyaW8gZGUgbG9zIApkZXJlY2hvcyB5IHF1ZSBlbiBkaWNobyBtYXRlcmlhbCwgZXN0w6EgY2xhcmFtZW50ZSBpZGVudGlmaWNhZGEgeSByZWNvbm9jaWRhIHN1IAphdXRvcsOtYSBkZW50cm8gZWwgdGV4dG8gbyBkZWwgY29udGVuaWRvIGRlIGRpY2hvIGRvY3VtZW50by4gCgpTaSBlbCBlbnbDrW8gc2UgYmFzYSBlbiB1biB0cmFiYWpvIHF1ZSBoYSBzaWRvIHBhdHJvY2luYWRvIG8gYXBveWFkbyBwb3IgdW5hIGFnZW5jaWEgCnUgb3JnYW5pemFjacOzbiBkaXN0aW50YSBhIFJFUElTQUxVRCwgdXN0ZWQgYWNlcHRhIHF1ZSBoYSBjdW1wbGlkbyBjb24gZWwgZGVyZWNobyBkZSAKcmV2aXNpw7NuIHkgb3RyYXMgb2JsaWdhY2lvbmVzIHJlcXVlcmlkYXMgcG9yIGNvbnRyYXRvIG8gYWN1ZXJkby4gCgpSRVBJU0FMVUQgaWRlbnRpZmljYXLDoSBjbGFyYW1lbnRlIHN1KHMpIG5vbWJyZShzKSBjb21vIGF1dG9yKHMpIG8gcHJvcGlldGFyaW8ocykgCmRlbCBkb2N1bWVudG8sIHkgbm8gaGFyw6EgbmluZ3VuYSBhbHRlcmFjacOzbiwgZXhjZXB0byBzZWfDum4gbG8gcGVybWl0aWRvIHBvciBlc3RhIApsaWNlbmNpYS4gCg==
URL
https://repisalud.isciii.es/bitstreams/21f609c6-3289-4be5-87f3-4245e6d205c8/download
File
MD5
1f9429a8a65f5cb707dff2782fbe3fab
4935191
application/pdf
Thesis Hector Sanchez-Iranzo..pdf
URL
https://repisalud.isciii.es/bitstreams/26f5aad1-dce3-4895-b067-d7edcd92c459/download
File
MD5
576161e901c992ebc982144fc0d968cd
12009
text/plain
Anexo 1. Supplementary File 1. tbx5tdTomato.txt
URL
https://repisalud.isciii.es/bitstreams/006847b8-81c7-48b1-8d8e-0d9bf8eaa00e/download
File
MD5
0aac94024a2e5868b40d23b3acc08465
11342
text/plain
Anexo 2. Supplementary File 2. mCherry_CreERT2.txt
URL
https://repisalud.isciii.es/bitstreams/ca64ddd2-aebc-4daa-a2f1-40c7ad8a3f77/download
File
MD5
aff099dd2eb127e8d9254af1e291aacd
13081
text/plain
Anexo 3. Supplementary File 3. iTol2Amp_Cryst_RFP.txt
URL
https://repisalud.isciii.es/bitstreams/c87d8dd6-6704-4801-9e22-1aad437b20fc/download
File
MD5
818fcbc2ae44042332aeef3ec1f1b511
12042
text/plain
Anexo 4. Supplementary File 4. loxP_tagBFP_loxP_mCherry-NTR.txt
URL
https://repisalud.isciii.es/bitstreams/e77e4f53-e496-4df6-b427-c10b579d7be3/download
File
MD5
91436d134369001aa41001214afedbfb
12207
text/plain
Anexo 5. Supplementary File 5. iTol2Amp_Cryst_GFP.txt
URL
https://repisalud.isciii.es/bitstreams/57f8c860-5f8e-42ef-9c55-20b7992ac4be/download
File
MD5
b0969b9b3fb07b9bbd4eee76089743b7
26234
text/plain
Anexo 6. Supplementary File 6. wt1a_CreERT2.txt
URL
https://repisalud.isciii.es/bitstreams/d1caa84b-14c6-4781-a5df-225416e2d59c/download
File
MD5
41ec93833d3fab2da6703835ab0ad69a
6498708
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Anexo 7. Supplementary Table 1. tbx5a RNA-Seq.xlsx
URL
https://repisalud.isciii.es/bitstreams/f13acf76-d323-4071-bfd8-c3964939238f/download
File
MD5
b7b02a1513a6631e606f12a2e7b2ede4
2166698
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Anexo 8. Supplementary Table 2. wt1a_GFP RNA-Seq.xlsx
URL
https://repisalud.isciii.es/bitstreams/1ed3778a-3fe0-4308-8fca-18c4907ea22d/download
File
MD5
10330cb64721c69181fc70abdd09bdb3
1987030
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Anexo 9. Supplementary Table 3. kdrl_mCherry RNA-Seq.xlsx
URL
https://repisalud.isciii.es/bitstreams/e5460a57-d622-4413-87a9-267b95ade678/download
File
MD5
132432efb777212b8cea1e0394887fb5
2444518
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Anexo 10. Supplementary Table 4. postn_citrine RNA-Seq.xlsx
URL
https://repisalud.isciii.es/bitstreams/cf9feb8f-bad1-4475-9841-a23415c195b4/download
File
MD5
3b67eacb7e2151642fde2e2d86f2d1e1
2154557
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Anexo 11. Supplementary Table 5. postn_CreERT2 RNA-Seq.xlsx
URL
https://repisalud.isciii.es/bitstreams/b9a453e8-9904-43c1-8704-0f1cb152ec55/download
File
MD5
acc336a10bac3319a702f23a5c41bd21
203063
text/plain
Thesis Hector Sanchez-Iranzo..pdf.txt
URL
https://repisalud.isciii.es/bitstreams/0ae70ac5-0f2e-4ef2-9920-d629bcace6ec/download
File
MD5
67c651979a649e4e18426ee45433fbcf
10276
text/plain
Anexo 1. Supplementary File 1. tbx5tdTomato.txt.txt
URL
https://repisalud.isciii.es/bitstreams/0840e21e-f01b-416b-81fe-74e1bdc115aa/download
File
MD5
0086b241f70f2f82c81daee88de562e5
9925
text/plain
Anexo 2. Supplementary File 2. mCherry_CreERT2.txt.txt
URL
https://repisalud.isciii.es/bitstreams/ea8060be-e562-402f-8b1f-49b35f0db5d6/download
File
MD5
27f8333fe42454763118691e578a19a0
10998
text/plain
Anexo 3. Supplementary File 3. iTol2Amp_Cryst_RFP.txt.txt
URL
https://repisalud.isciii.es/bitstreams/0ba817c2-a41d-4240-9a04-f5370cbcd140/download
File
MD5
be174fba5fa17c7db19d993b53974b05
10260
text/plain
Anexo 4. Supplementary File 4. loxP_tagBFP_loxP_mCherry-NTR.txt.txt
URL
https://repisalud.isciii.es/bitstreams/ad34a4cc-acbd-4e9d-ba21-3cbb985dd22d/download
File
MD5
114536d9323b829cfa56919aa5a2dfb9
10395
text/plain
Anexo 5. Supplementary File 5. iTol2Amp_Cryst_GFP.txt.txt
URL
https://repisalud.isciii.es/bitstreams/b90e2b5f-58a9-4ed5-bcaf-0303667c4ea7/download
File
MD5
00273cc341bc52363369d25a4eb98515
22534
text/plain
Anexo 6. Supplementary File 6. wt1a_CreERT2.txt.txt
URL
https://repisalud.isciii.es/bitstreams/404c7237-e521-44ca-bb91-bff381d03e67/download
File
MD5
eda8939f09649dc242eb8cc41ef44c58
100000
text/plain
Anexo 7. Supplementary Table 1. tbx5a RNA-Seq.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/a166cec2-6b2c-42a1-b435-7c3b267757f6/download
File
MD5
16383b491dc9a01917a4977648cd2ffd
100000
text/plain
Anexo 8. Supplementary Table 2. wt1a_GFP RNA-Seq.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/fac645d8-abb2-401c-b3f9-ced2cc322443/download
File
MD5
2be33b3d8ef31d251e2124654d9dcb25
100000
text/plain
Anexo 9. Supplementary Table 3. kdrl_mCherry RNA-Seq.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/769b345c-19cd-479c-85cf-a977554d73a1/download
File
MD5
41f8aa63b7884150c6b1dc9b8284e090
100000
text/plain
Anexo 10. Supplementary Table 4. postn_citrine RNA-Seq.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/9a907d8f-ec24-4133-a58f-c68ad954428e/download
File
MD5
efc673ffa6199e4e9284037c79ce10bd
100000
text/plain
Anexo 11. Supplementary Table 5. postn_CreERT2 RNA-Seq.xlsx.txt